https://www.fiercebiotech.com/research/extending-use-car-t-cells-lupus
Genetically engineered immune cells wipe out lupus in mice
https://www.sciencemag.org/news/2019/03/genetically-engineered-immune-cells-wipe-out-lupus-mice
Full high-throughput sequencing analysis of differences in expression profiles of long noncoding RNAs and their mechanisms of action in systemic lupus erythematosus
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-1853-7
https://www.ncbi.nlm.nih.gov/pubmed/30836987?dopt=Abstract
Related Articles
Full high-throughput sequencing analysis of differences in expression profiles of long noncoding RNAs and their mechanisms of action in systemic lupus erythematosus.
Arthritis Res Ther. 2019 Mar 05;21(1):70
Authors: Ye H, Wang X, Wang L, Chu X, Hu X, Sun L, Jiang M, Wang H, Wang Z, Zhao H, Yang X, Wang J
Abstract
BACKGROUND: The specific function of long noncoding RNAs (lncRNAs) in systemic lupus erythematosus (SLE) and the mechanism of their involvement in related pathological changes remain to be elucidated, so, in this study, we analyzed the differences in the expression profiles of lncRNAs and their mechanisms of action in SLE using full high-throughput sequencing, bioinformatics, etc. methods.
METHODS: We used high-throughput sequencing to detect differences in the expression profiles of lncRNAs, miRNAs, and mRNAs in PBMCs from patients with SLE at the genome-wide level. Next, we predicted target genes of 30 lincRNAs (long intergenic noncoding RNAs) by constructing a coexpression network of differential lincRNAs and mRNAs and identified the role of lincRNAs. Then, we analyzed the coexpression network of 23 optimized lincRNAs and their corresponding 353 miRNAs, evaluated the cis- and trans-effects of these lincRNAs, and performed GO and KEGG analyses of target genes. We also selected 8 lincRNAs and 2 newly discovered lncRNAs for q-PCR validation and lncRNA-miRNA-mRNA analysis. Finally, we also analyzed respectively the relation between lncRNAs and gender bias in SLE patients using RT-qPCR, the relation between Systemic Lupus Erythematosus Disease Activity Index score and the “IFN signature” using ELISA, and the relation between the differential expression of lncRNAs and a change in the number of a cell type of PBMCs in SLE patients using RT-qPCR.
RESULTS: The profiles of 1087 lncRNAs, 102 miRNAs, and 4101 mRNAs in PBMCs significantly differed between patients with SLE and healthy controls. The coexpression network analysis showed that the network contained 23 lincRNAs and 353 mRNAs. The evaluation of the cis- and trans-effects showed that the 23 lincRNAs acted on 704 target genes. GO and KEGG analyses of the target genes predicted the biological functions of the 23 lincRNAs. q-PCR validation showed 7 lincRNAs and 2 novel lncRNAs were identical to the sequencing results. The ceRNA network contained 7 validated lincRNAs, 15 miRNAs, and 155 mRNAs. In addition, the differential expression of lncRNAs may be gender dependent in SLE patients, SLE patients also exhibit a robust “IFN signature,” and PBMCs exhibiting differential expression of lncRNAs may be due to a change in the number of a cell type.
CONCLUSION: This work determined specific lncRNAs that play important biological functions in the pathogenesis of lupus and provided a new direction for diagnosis and treatment of disease.
PMID: 30836987 [PubMed – in process]
PubMed:30836987
ILT-101 in Patients With Active Moderate to Severe Systemic Lupus Erythematosus (SLE)
https://clinicaltrials.gov/ct2/show/NCT02955615?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F19%2F2019&lupd_d=14
Free light chains and chronic autoimmune-based inflammatory diseases
https://www.sciencedirect.com/science/article/abs/pii/S1568997219300564?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30844547?dopt=Abstract
Free light chains and autoimmunity.
Autoimmun Rev. 2019 Mar 04;:
Authors: Napodano C, Pocino K, Rigante D, Stefanile A, Gulli F, Marino M, Basile V, Rapaccini GL, Basile U
Abstract
The study of free light chains (FLCs) has grown as area of enormous interest for many clinicians with the aim of disclosing the exact biological role and potential use of FLCs in the clinical routine. Moreover, the attention given to immunological functions of FLCs has sparked a new light into their pathogenic contribution in different chronic autoimmune-based inflammatory diseases. The release of intracellular antigens following cell death or ineffective clearance of apoptotic debris, modification of self-antigens, and molecular mimicry may trigger the production of immunoglobulins after activation and polyclonal expansion of B cells, by which FLCs are released. The discovery of polyclonal FLCs as potential biomarkers started with the observation of their increased concentrations in a variety of biological fluids related to patients with autoimmune diseases. This review deals with the use of polyclonal FLCs for identifying severity and monitoring outcome after treatment in some autoimmune diseases, namely systemic lupus erythematosus, myasthenia gravis, systemic sclerosis, rheumatoid arthritis and Sjögren’s syndrome, as supported by the fact that levels of FLCs correlate with both B cell activation markers and other specific markers of disease activity. In a near future, following the evidence shown, FLCs might probably work as early prognostic markers of severity and also as indicators of response to treatment or early assessment of relapse in selected autoimmune diseases.
PMID: 30844547 [PubMed – as supplied by publisher]
PubMed:30844547
Lupus Therapeutics partners with Takeda on phase 1 trial to evaluate TAK-079 as potential new therapy for lupus
https://www.ptcommunity.com/wire/lupus-therapeutics-partners-takeda-phase-1-trial [Read more…] about Lupus Therapeutics partners with Takeda on phase 1 trial to evaluate TAK-079 as potential new therapy for lupus
Positive Early Results for BIIB059 as New Treatment Strategy
Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT02908100?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F14%2F2019&lupd_d=14
Protective role of anti-ribosomal P antibody in patients with lupus nephritis
https://www.ncbi.nlm.nih.gov/pubmed/30809965
Related Articles
Protective role of anti-ribosomal P antibody in patients with lupus nephritis.
Int J Rheum Dis. 2019 Feb 27;:
Authors: Kang JH, Park DJ, Choi SE, Yim YR, Kim JE, Lee JW, Lee KE, Kim TJ, Park YW, Lee JS, Choi YD, Lee JK, Lee SS
Abstract
AIM: The aim of this study was to define clinical, histopathologic, and prognostic differences according to the presence of anti-ribosomal P antibody (anti-P) in Korean patients with biopsy-proven lupus nephritis (LN).
METHODS: We studied 79 patients who underwent kidney biopsies prior to the start of induction treatment, and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than 6 months. Anti-P was measured by immunoblot analysis at the time of renal biopsy.
RESULTS: Of all patients, 35.4% were anti-P-positive. Such patients exhibited earlier LN onset, a higher Systemic Lupus Erythematosus Disease Activity Index 2000 score, and a higher estimated glomerular filtration rate at the time of renal biopsy, than did those without antibodies. Upon renal histopathological analysis, patients with anti-P exhibited less interstitial inflammation in terms of the activity index, less glomerular sclerosis, less tubular atrophy, and less interstitial fibrosis in terms of the chronicity index. Furthermore, anti-P was associated with lower chronicity scores. At a median follow-up time of 47 months, renal function was preserved in 27 of 28 patients who had anti-P, but only 38 of 51 patients without such antibodies did not progress to chronic renal disease. After multivariate logistic regression, we found that anti-P positivity was associated with a reduced rate of progression to chronic kidney disease after adjusting for gender, baseline creatinine, activity and chronicity score, and treatment response (odds ratio = 0.196, 95% CI: 0.039-0.989, P = 0.048).
CONCLUSION: Anti-P was associated with better histological findings, and anti-P-positive patients had better renal outcomes than those without anti-P.
PMID: 30809965 [PubMed – as supplied by publisher]
PubMed:30809965
Equillium Announces Plan to Develop EQ001 for the Treatment of Lupus Nephritis
https://globenewswire.com/news-release/2019/02/26/1742914/0/en/Equillium-Announces-Plan-to-Develop-EQ001-for-the-Treatment-of-Lupus-Nephritis.html
Exagen and the Lupus Foundation of America Partner on New Initiative to Reduce the Time to an Accurate Lupus Diagnosis
https://www.lupus.org/news/exagen-and-the-lupus-foundation-of-america-partner-on-new-initiative-to-reduce-the-time-to-an-accurate-lupus-diagnosis
A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT02349061?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F11%2F2019&lupd_d=14
Condition : Lupus Erythematosus, Systemic
Interventions : Drug: Ustekinumab IV; Drug: Placebo Infusion; Drug: Placebo SC; Drug: Ustekinumab SC; Other: Concomitant Medication
Sponsor : Janssen Research & Development, LLC
Active, not recruiting
A Phase 2a, Efficacy and Safety Study of Ustekinumab in Systemic Lupus Erythematosus
NCT02349061
Wed, 28 Jan 2015 12:00:00 EST
Potential for cannabinoid receptor 2 (CB2) targeted therapeutics for treatment of inflammatory conditions involving aberrant pDC activity such as systemic lupus erythematosus and rheumatoid arthritis
Collectively, these results demonstrate the potential for CB2 targeted therapeutics for treatment of inflammatory conditions involving aberrant pDC activity.
https://www.sciencedirect.com/science/article/pii/S0041008X19300705?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30807757?dopt=Abstract
Suppression of CpG-ODN-mediated IFNα and TNFα response in human plasmacytoid dendritic cells (pDC) by cannabinoid receptor 2 (CB2)-specific agonists.
Toxicol Appl Pharmacol. 2019 Feb 23;:
Authors: Henriquez JE, Crawford RB, Kaminski NE
Abstract
Plasmacytoid dendritic cells (pDC) compose 0.2-0.5% of circulating leukocytes but play a significant role in mounting host immune responses. Elevated and chronic activation of pDC are implicated in autoimmune disease like systemic lupus erythematosus and rheumatoid arthritis. Δ9-tetrahydrocannabinol (THC) is a well characterized cannabinoid with potent anti-inflammatory activity, but acceptance of THC as a treatment for autoimmune disorders has been hindered due to psychotropic activity. The psychotropic effects of THC are mediated through cannabinoid receptor 1 (CB1) expressed in the central nervous system while the immunomodulatory effects of THC result from THC binding to CB1 and CB2 on immune cells. Synthetic CB2-selective agonists have been developed to explore immune modulation by cannabinoids in the absence of psychotropic effects. The goal of these studies was to determine if the CB2-selective agonists, JWH-015 and JWH-133, have comparable efficacy to THC in modulating IFNα and TNFα responses by primary human pDC. Treatment with JWH-133 and JWH-015 inhibited CpG-induced IFNα and TNFα responses by pDC. Further, the phosphorylation of IRF7, TBK1, NFκB, and IKKγ, key events in pDC activation, were suppressed by THC, JWH-133, and JWH-015. Likewise, the phosphorylation of AKT at the S473 and T308 residues were differentially modulated by treatment with THC and both JWH compounds. Collectively, these results demonstrate the potential for CB2 targeted therapeutics for treatment of inflammatory conditions involving aberrant pDC activity.
PMID: 30807757 [PubMed – as supplied by publisher]
PubMed:30807757
Immunological pathogenesis and treatment of systemic lupus erythematosus
https://link.springer.com/article/10.1007%2Fs12519-019-00229-3
https://www.ncbi.nlm.nih.gov/pubmed/30796732?dopt=Abstract
Related Articles
Immunological pathogenesis and treatment of systemic lupus erythematosus.
World J Pediatr. 2019 Feb 22;:
Authors: Pan L, Lu MP, Wang JH, Xu M, Yang SR
Abstract
BACKGROUND: Systemic lupus erythematosis (SLE) is a complex and clinically heterogeneous autoimmune disease. A variety of immunological defects contribute to SLE, including dysregulated innate and adaptive immune response. A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment. The aim of this review was to clarify the immunological pathogenesis and treatment of SLE.
DATA SOURCES: Literature reviews and original research articles were collected from database, including PubMed and Wanfang. Relevant articles about SLE were included.
RESULTS: Breakdown of self-tolerance is the main pathogenesis of SLE. The innate and adaptive immune networks are interlinked with each other through cytokines, complements, immune complexes and kinases of the intracellular machinery. Treatments targeted at possible targets of immunity have been assessed in clinical trials. Most of them did not show better safety and efficacy than traditional treatments. However, novel targeting treatments are still being explored.
CONCLUSIONS: Dysregulated immune response plays a critical role in SLE, including innate immunity and adaptive immunity. Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.
PMID: 30796732 [PubMed – as supplied by publisher]
PubMed:30796732
Effect of Anti-BDCA2 mAb Treatment (BIIB059) on pDC IFNα Production From Patients Affected With Cutaneous Lupus Erythematosus
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00275/full
https://www.ncbi.nlm.nih.gov/pubmed/30846987?dopt=Abstract
Related Articles
Effect of in vivo Hydroxychloroquine and ex vivo Anti-BDCA2 mAb Treatment on pDC IFNα Production From Patients Affected With Cutaneous Lupus Erythematosus.
Front Immunol. 2019;10:275
Authors: Gardet A, Pellerin A, McCarl CA, Diwanji R, Wang W, Donaldson D, Franchimont N, Werth VP, Rabah D
Abstract
Objective: Plasmacytoid dendritic cells (pDCs) are a major source of Type-I Interferon (IFN-I), a key driver in cutaneous lupus erythematosus (CLE). Currently evaluated in Phase II clinical trial, 24F4A (BIIB059) is an antibody targeting BDCA2, an inhibitory receptor expressed on pDCs. Given that Hydroxychloroquine (HCQ), a widely-used CLE therapy, and 24F4A are both able to inhibit pDC-derived IFN-I production; this study aimed to determine whether 24F4A would show an additional inhibitory effect on pDC response after ex vivo or in vivo treatment with HCQ. Methods: The effect of 24F4A on pDC-derived IFNα was measured from peripheral blood mononuclear cells (PBMC) either from healthy donors in presence or absence of HCQ or from CLE patients clinically exposed to various levels of HCQ. TLR7, TLR7/8, and TLR9 agonists (ssRNA, R848, and CpG-A) were used for pDC stimulation. Results: PDCs were the only producers of IFNα in response to CpG-A, R848, and ssRNA stimulation in PBMC cultures. CLE patients with higher levels of blood HCQ showed lower ex vivo pDC responses to CpG-A, but not R848 or ssRNA. In contrast, 24F4A reduced the amount of IFNα produced by pDCs from CLE patients in response to all TLR agonists, irrespective of the blood HCQ level. Conclusion: Our findings reveal that clinically-relevant HCQ concentrations partially inhibit the pDC response to TLR9 and weakly affect the response to TLR7/8 stimulation. 24F4A robustly inhibits pDC responses even in the presence of HCQ, highlighting its unique potential to disrupt pDC disease relevant biology, which could provide additional therapeutic benefit for CLE patients.
PMID: 30846987 [PubMed – in process]
PubMed:30846987
Clinical Experience of Sirolimus Regarding Efficacy and Safety in Systemic Lupus Erythematosus
https://www.frontiersin.org/articles/10.3389/fphar.2019.00082/full
https://www.ncbi.nlm.nih.gov/pubmed/30787878?dopt=Abstract
Related Articles
Clinical Experience of Sirolimus Regarding Efficacy and Safety in Systemic Lupus Erythematosus.
Front Pharmacol. 2019;10:82
Authors: Eriksson P, Wallin P, Sjöwall C
Abstract
New treatment options constitute unmet needs for patients diagnosed with systemic lupus erythematosus (SLE). Inhibition of the mammalian target of rapamycin (mTOR) pathway by sirolimus, a drug approved and in clinical use to prevent transplant rejection, has shown promising effects in lupus animal models as well as in patients with both antiphospholipid syndrome and SLE. Sirolimus inhibits antigen-induced T cell proliferation and increases the number of circulating regulatory T cells. Recently, sirolimus was tested in an open label phase 1/2 trial, including 43 patients with active SLE, resistant or intolerant to conventional medications. The results were encouraging showing a progressive improvement, including mucocutaneous and musculoskeletal manifestations. At our university unit, we have more than 16 years’ experience of sirolimus as treatment for non-renal manifestations of SLE. Herein, we retrospectively evaluated data on tolerance, dosage, affected organ systems, disease activity measures, corticosteroid reduction, concomitant immunosuppressive therapies, and patient-reported outcome measures (PROMs) such as pain intensity, fatigue, well-being and quality-of-life (QoL) in 27 Caucasian patients with mildly active SLE. Musculoskeletal manifestation was the main reason for sirolimus treatment followed by skin involvement and leukocytopenia. Mean time on sirolimus was 47.1 (range 2-140) months. Decreasing global disease activity was observed, as measured by the clinical SLE disease activity index-2000, with a mean reduction of 2.5 points (range -10 to 0) and a corresponding mean reduction of the physician’s global assessment (0-4) of 0.64 (range -2 to 0). The mean daily dose of corticosteroids (prednisolone) was reduced by 3.3 mg (-12.5 to 0). Non-significant trends toward improvements of QoL and pain intensity were found. Serious side-effects were not seen during sirolimus treatment, but early withdrawal due to nausea (n = 4) and non-serious infections (n = 2) appeared. This observational study, including longtime real-life use of sirolimus in SLE, is the largest to date and it essentially confirms the results of the recent phase 1/2 trial. Our data indicate that sirolimus is efficient in patients with musculoskeletal SLE manifestations, particularly arthritis and tendinitis. Further randomized controlled trials evaluating the potential benefits of sirolimus in SLE are warranted, but should aim to enroll patients with shorter disease duration, less accrued damage, and more diverse ethnicities.
PMID: 30787878 [PubMed]
PubMed:30787878
Pim-1 as a therapeutic target in human lupus nephritis – “targeting Pim-1/NFATc1/NLRP3 pathway might be a therapy for human lupus nephritis … mice were used to confirm the therapeutic effects of Pim-1 inhibition”
These data identify Pim-1 as a critical regulator of LN pathogenesis and targeting Pim-1/NFATc1/NLRP3 pathway might be a therapy for human LN.
https://www.ncbi.nlm.nih.gov/pubmed/30791224?dopt=Abstract
https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40863
Safety and Efficacy of Filgotinib and GS-9876 in Females With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)
https://clinicaltrials.gov/ct2/show/NCT03134222?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F07%2F2019&lupd_d=14
Condition : Cutaneous Lupus Erythematosus
Interventions : Drug: Filgotinib; Drug: GS-9876; Drug: Filgotinib placebo; Drug: GS-9876 placebo
Sponsors : Gilead Sciences; Galapagos NV
Active, not recruiting
Safety and Efficacy of Filgotinib and GS-9876 in Females With Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)
NCT03134222
Fri, 28 Apr 2017 12:00:00 EDT
Study to Evaluate BIIB059 in Cutaneous Lupus Erythematosus (CLE) With or Without Systemic Lupus Erythematosus (SLE)
https://clinicaltrials.gov/ct2/show/NCT02847598?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F06%2F2019&lupd_d=14
Conditions : Systemic Lupus Erythematosus; Active Cutaneous Lupus Erythematosus
Interventions : Drug: BIIB059; Drug: Placebo
Sponsor : Biogen
Recruiting
Study to Evaluate BIIB059 in Cutaneous Lupus Erythematosus (CLE) With or Without Systemic Lupus Erythematosus (SLE)
NCT02847598
Thu, 28 Jul 2016 12:00:00 EDT
Last Update Posted: February 20, 2019
Bacteria in the Gut May be a Cause of Lupus, Shows Study Supported by Lupus Research Alliance
https://www.prnewswire.com/news-releases/bacteria-in-the-gut-may-be-a-cause-of-lupus-300798166.html
Lupus strongly linked to imbalances in gut microbiome
https://eurekalert.org/pub_releases/2019-02/nlh-lsl021319.php
Helminth-Based Product and the Microbiome of Mice with Lupus – “This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus”
https://msystems.asm.org/content/4/1/e00160-18/article-info
https://www.ncbi.nlm.nih.gov/pubmed/30801028?dopt=Abstract
Related Articles
Helminth-Based Product and the Microbiome of Mice with Lupus.
mSystems. 2019 Jan-Feb;4(1):
Authors: Neuman H, Mor H, Bashi T, Givol O, Watad A, Shemer A, Volkov A, Barshack I, Fridkin M, Blank M, Shoenfeld Y, Koren O
Abstract
The hygiene hypothesis claims that the lack of exposure to microorganisms in developed countries correlates with a rise in the incidence of autoimmune diseases. It was also found that helminths are able to modulate the immune response in hosts in order to survive. Consequently, several successful trials using helminths as a treatment for autoimmune patients have been reported. The helminth derivative, phosphorylcholine (PC), was discovered as an immunomodulatory molecule. We have recently shown in a murine model that when a conjugate of tuftsin and PC, termed TPC, is prophylactically administered before the onset of glomerulonephritis, it attenuates the development of systemic lupus erythematosus (SLE). The current study aimed to examine the TPC effect on the gut microbiome in a mouse model of lupus. TPC treatment altered the gut composition in the mice with active lupus, in correlation with a significant decrease in glomerulonephritis, followed by an increased level of anti-inflammatory interleukin 10 (IL-10), decreased levels of proinflammatory mediators, and expansion of the T regulatory cell population. Importantly, we found that TPC treatment altered the mouse gut microbiome composition, in correlation with a significant decrease in protein secretion and improved disease parameters. The major effects of TPC treatment on the gut microbiome included decreased abundances of Akkermansia and increased abundance of several genera, including Turicibacter, Bifidobacterium, unclassified Mogibacteriaceae, unclassified Clostridiaceae, Adlercreutzia, Allobaculum, and Anaeroplasma. Overall, our results associate microbial changes with the immunomodulation of glomerulonephritis in mice with lupus. IMPORTANCE Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following tuftsin and phosphorylcholine treatment.
PMID: 30801028 [PubMed]
PubMed:30801028
IMPORTANCE Recently, several papers referred to the association of different bacteria with lupus in mice and humans. This is the first report to demonstrate the effect of a compound derived from helminths on the induction of remission in mice with lupus and its association with a bacterial change. We show that several genera, including Akkermansia, are associated with clinical and serological parameters of lupus, while other genera, including butyrate-producing bacteria, are associated with amelioration of disease following tuftsin and phosphorylcholine treatment.
A DOSE-RANGING STUDY TO EVALUATE EFFICACY AND SAFETY OF PF-06700841 IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
https://clinicaltrials.gov/ct2/show/NCT03845517?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F05%2F2019&lupd_d=14
Condition : Systemic Lupus Erythematosus
Interventions : Drug: Placebo; Drug: PF-06700841 15 mg; Drug: PF-06700841 30 mg; Drug: PF-06700841 45 mg
Sponsor : Pfizer
Not yet recruiting
A DOSE-RANGING STUDY TO EVALUATE EFFICACY AND SAFETY OF PF-06700841 IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
NCT03845517
Tue, 19 Feb 2019 12:00:00 EST
A promising approach to targeting type 1 IFN in systemic lupus erythematosus
https://www.jci.org/articles/view/127101 [Read more…] about A promising approach to targeting type 1 IFN in systemic lupus erythematosus
Development of an ICOSL and BAFF bispecific inhibitor AMG 570 for systemic lupus erythematosus treatment
By targeting both ICOSL and BAFF, AMG 570 has the potential to achieve superior efficacy in treatment of autoimmune diseases such as SLE and rheumatoid arthritis.
https://www.ncbi.nlm.nih.gov/pubmed/30789152?dopt=Abstract
Related Articles
Development of an ICOSL and BAFF bispecific inhibitor AMG 570 for systemic lupus erythematosus treatment.
Clin Exp Rheumatol. 2019 Feb 15;
Authors: Zhang M, Lee F, Knize A, Jacobsen F, Yu S, Ishida K, Miner K, Gaida K, Whoriskey J, Chen C, Gunasekaran K, Hsu H
Abstract
OBJECTIVES: Systemic lupus erythematous (SLE) is a heterogeneous disease lacking highly effective treatment options. Here we tested if targeting both BAFF and ICOSL has superior efficacy than single target inhibition in the mouse arthritis and lupus models. We also generated AMG 570, an ICOSL and BAFF bispecific inhibitory molecule, for potential treatment of autoimmune diseases such as SLE.
METHODS: Murine BAFF/ICOSL bispecific, combination of BAFF and ICOSL inhibitors or single inhibitor was evaluated in the sheep red blood cell (SRBC) challenge model, mouse collagen induced arthritis (CIA) model, or NZB/NZW lupus models. AMG 570 was tested for human and cyno BAFF and ICOSL binding affinities by Kinexa A. AMG 570 dual target blocking activities was evaluated in human and cyno BAFF and ICOSL mediated B cell and T cell assay, respectively. Pharmacodynamics effect of AMG 570 was evaluated in cynomolgus monkey.
RESULTS: Treatment with murine ICOSL/BAFF bispecific or combination therapy was more efficacious than single ICOSL or BAFF inhibitor in mouse NZB/NZW lupus model. Dual ICOSL and BAFF inhibition was also more effective in the mouse collagen induced arthritis (CIA) model. AMG 570 was developed as the clinical bispecific lead. AMG 570 inhibits human and cynomolgus monkey ICOSL and BAFF. B cell reduction was observed after AMG 570 treatment in cynomolgus monkeys, consistent with the pharmacological effect of BAFF inhibition.
CONCLUSIONS: By targeting both ICOSL and BAFF, AMG 570 has the potential to achieve superior efficacy in treatment of autoimmune diseases such as SLE and rheumatoid arthritis.
PMID: 30789152 [PubMed – as supplied by publisher]
PubMed:30789152
Potential drug therapies persist amid ‘lupus trial graveyard’
https://www.healio.com/rheumatology/lupus/news/online/%7B42aae2d4-0d86-49f6-ac97-9ae0879c98db%7D/potential-drug-therapies-persist-amid-lupus-trial-graveyard
Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT02794285?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F01%2F2019&lupd_d=14
Condition : Active Systemic Lupus Erythematosus
Interventions : Biological: Anifrolumab; Drug: Placebo
Sponsors : AstraZeneca; PRA Health Sciences
Active, not recruiting
Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
NCT02794285
Thu, 09 Jun 2016 12:00:00 EDT
Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Lupus Nephritis
https://clinicaltrials.gov/ct2/show/NCT03610516?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F01%2F2019&lupd_d=14
Condition : Lupus Nephritis
Interventions : Drug: CFZ533; Drug: Placebo
Sponsor : Novartis Pharmaceuticals
Recruiting
Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Lupus Nephritis.
NCT03610516
Wed, 01 Aug 2018 12:00:00 EDT
An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT03407482?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F01%2F2019&lupd_d=14
Condition : Lupus Erythematosus, Systemic
Intervention : Drug: GDC-0853
Sponsor : Genentech, Inc.
Recruiting
An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
NCT03407482
Tue, 23 Jan 2018 12:00:00 EST
A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (SLE)
https://clinicaltrials.gov/ct2/show/NCT03843125?type=Intr&cond=Lupus&phase=012345&lupd_s=02%2F01%2F2019&lupd_d=14
Condition : Systemic Lupus Erythematosus
Intervention : Drug: Baricitinib
Sponsors : Eli Lilly and Company; Incyte Corporation
Not yet recruiting
A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (SLE)
NCT03843125
Fri, 15 Feb 2019 12:00:00 EST
B Cells as a Therapeutic Target in Paediatric Rheumatic Disease – “rationale behind the use of B cell-targeted therapies in Juvenile Systemic Lupus Erythematosus (JSLE)”
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00214/full
https://www.ncbi.nlm.nih.gov/pubmed/30837988?dopt=Abstract
B Cells as a Therapeutic Target in Paediatric Rheumatic Disease.
Front Immunol. 2019;10:214
Authors: Wilkinson MGL, Rosser EC
Abstract
B cells carry out a central role in the pathogenesis of autoimmune disease. In addition to the production of autoantibodies, B cells can contribute to disease development by presenting autoantigens to autoreactive T cells and by secreting pro-inflammatory cytokines and chemokines which leads to the amplification of the inflammatory response. Targeting both the antibody-dependent and antibody-independent function of B cells in adult rheumatic disease has led to the advent of B cell targeted therapies in clinical practice. To date, whether B cell depletion could also be utilized for the treatment of pediatric disease is relatively under explored. In this review, we will discuss the role of B cells in the pathogenesis of the pediatric rheumatic diseases Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (JSLE) and Juvenile Dermatomyositis (JDM). We will also explore the rationale behind the use of B cell-targeted therapies in pediatric rheumatic disease by highlighting new case studies that points to their efficacy in JIA, JSLE, and JDM.
PMID: 30837988 [PubMed – in process]
PubMed:30837988
Podocytes and autophagy: A potential therapeutic target in lupus nephritis
https://www.tandfonline.com/doi/abs/10.1080/15548627.2019.1580512?journalCode=kaup20
https://www.ncbi.nlm.nih.gov/pubmed/30755075?dopt=Abstract
Podocytes and autophagy: A potential therapeutic target in lupus nephritis.
Autophagy
Related Articles
Podocytes and autophagy: A potential therapeutic target in lupus nephritis.
Autophagy. 2019 Feb 13;:
Authors: Zhou XJ, Klionsky DJ, Zhang H
Abstract
Recent studies suggest that defects in macroautophagy/autophagy contribute to the pathogenesis of systemic lupus erythamatosus (SLE), especially in adaptive immunity. The occurrence and progression of lupus nephritis (LN) is the end result of complex interactions between regulation of immune responses and pathological process by renal resident cells, but there is still a lot of missing information for establishing the role of autophagy in the pathogenesis of LN, and as a therapy target. In our recent study, we observed that autophagy is activated in LN, especially in podocytes. Based on in vitro assays, many of the most important mediators of the disease-patients’ sera, patients’ IgG and IFNA/IFN-α-can induce autophagy in both murine and human podocytes, by reactive oxygen species production or MTORC1 inhibition; autophagy activation negatively associates with podocyte injury. With regard to intervention, autophagy activators can protect against podocyte injury, whereas autophagy inhibitors aggravate injury. Taken together, our findings suggest that podocyte autophagy is involved in lupus renal protection and may be a therapeutic target. These data shed new light on the role of rapamycin and autophagy inducers in the treatment of SLE.
PMID: 30755075 [PubMed – as supplied by publisher]
PubMed:30755075
Baicalin and ex vivo expanded Foxp3+ regulatory T cells are promising therapeutics for the treatment of lupus
https://www.nature.com/articles/s41419-019-1315-9
https://www.ncbi.nlm.nih.gov/pubmed/30760702?dopt=Abstract
Baicalin ameliorates lupus autoimmunity by inhibiting differentiation of Tfh cells and inducing expansion of Tfr cells.
Cell Death Dis
Related Articles
Baicalin ameliorates lupus autoimmunity by inhibiting differentiation of Tfh cells and inducing expansion of Tfr cells.
Cell Death Dis. 2019 Feb 13;10(2):140
Authors: Yang J, Yang X, Yang J, Li M
Abstract
Baicalin is a natural compound isolated from Chinese herb, which has been reported as an anti-inflammatory drug. Here, we demonstrated that Baicalin treatment could reduce urine protein, inhibit anti-ds-DNA antibody titers, and ameliorate lupus nephritis in MRL/lpr lupus-prone mice. Baicalin inhibited Tfh cell differentiation and IL-21 production, but promoted Foxp3+ regulatory T cell differentiation including part of follicular regulatory T (Tfr) cells. Intravenous injection of Baicalin-induced Foxp3+ regulatory T cells could relieve nephritis, inhibit Tfh cell differentiation and IL-21 production. Baicalin inhibited mTOR activation, reduced mTOR agonist-mediated Tfh cell expansion and increased Tfr cells. These data suggest that Baicalin attenuates lupus autoimmunity by up- and downregulating the differentiation of Tfr cells and Tfh cells, respectively. Baicalin and ex vivo expanded Foxp3+ regulatory T cells are promising therapeutics for the treatment of lupus.
PMID: 30760702 [PubMed – in process]
PubMed:30760702
IFM Therapeutics launches new spinout aimed at Parkinson’s, lupus and other diseases
https://www.bizjournals.com/boston/news/2019/02/11/ifm-therapeutics-launches-new-spinout-aimed-at.html
IFM Therapeutics launches new spinout aimed at Parkinson’s, lupus and other diseases
Role of PPAR-y Agonists in Immunomodulation and Vascular Prevention in SLE (PPAR-SLE)
https://clinicaltrials.gov/ct2/show/NCT02338999?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F28%2F2019&lupd_d=14
Condition : Systemic Lupus Erthematosus
Interventions : Radiation: PET/CT; Drug: Pioglitazone; Procedure: Vascular function studies
Sponsor : National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Recruiting
Role of PPAR-y Agonists in Immunomodulation and Vascular Prevention in SLE (PPAR-SLE)
NCT02338999
Thu, 15 Jan 2015 12:00:00 EST
>>> Updated February 11, 2019
Defective regulations that emerge from B cells of systemic lupus erythematosus patients can be restored by GA stimulation
http://www.jimmunol.org/content/early/2019/02/08/jimmunol.1801235
https://www.ncbi.nlm.nih.gov/pubmed/30745460?dopt=Abstract
Glatiramer Acetate Stimulates Regulatory B Cell Functions.
J Immunol
Related Articles
Glatiramer Acetate Stimulates Regulatory B Cell Functions.
J Immunol. 2019 Feb 11;:
Authors: Amrouche K, Pers JO, Jamin C
Abstract
The control of the activities of regulatory B (Breg) cells in immune disorders is an emerging therapeutic strategy for the recovery of immune homeostasis. Manipulating B cells using numerous drugs in vivo affect their regulatory functions, although a direct link has not yet been demonstrated. Glatiramer acetate (GA) is a synthetic polypeptide that is used in the treatment of inflammatory and autoimmune diseases. We experimented on an in vitro coculture system to determine its direct effects on the Breg cell properties of human B cells. We found that GA improves the B cell-dependent control of T cells’ immune responses. When B cells are stimulated by GA, the T cell proliferation and their Th1 IFN-γ production are further inhibited, whereas the B cell production of IL-10 is further enhanced. GA binds preferentially to the memory B cells and the activation of sorted B cell subsets shows that GA-dependent increased Breg cell activities are specifically supported by the B cells’ memory compartment. Moreover, we found that the defective regulations that emerge from the B cells of systemic lupus erythematosus patients can be restored by GA stimulation. Overall, these data demonstrate that GA stimulates the Breg functions mainly by shifting the memory B cells known to contribute to the T cell-dependent inflammatory response into Breg cells. Our results also indicate that GA treatment could be a useful therapy for recovering the Breg cells in autoimmune situations in which their activities are defective.
PMID: 30745460 [PubMed – as supplied by publisher]
PubMed:30745460
Changing paradigms in the treatment of systemic lupus erythematosus
https://lupus.bmj.com/content/6/1/e000310
Changing paradigms in the treatment of systemic lupus erythematosus
Safety and Efficacy of Filgotinib and GS-9876 in Adults With Lupus Membranous Nephropathy (LMN)
https://clinicaltrials.gov/ct2/show/NCT03285711?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F25%2F2019&lupd_d=14
Condition : Lupus Membranous Nephropathy
Interventions : Drug: Filgotinib; Drug: GS-9876; Drug: Filgotinib placebo; Drug: GS-9876 placebo
Sponsor : Gilead Sciences
Active, not recruiting
Safety and Efficacy of Filgotinib and GS-9876 in Adults With Lupus Membranous Nephropathy (LMN)
NCT03285711
Mon, 18 Sep 2017 12:00:00 EDT
>>> updated February 8, 2019
Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide
NAM may be a novel therapeutic option that improves kidney injury and pregnancy outcomes, thereby benefiting pregnant patients with SLE.
https://www.sciencedirect.com/science/article/pii/S0006291X19301391?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30739788?dopt=Abstract
Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide.
Biochem Biophys Res Commun
Related Articles
Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide.
Biochem Biophys Res Commun. 2019 Feb 07;:
Authors: Imaruoka K, Oe Y, Fushima T, Sato E, Sekimoto A, Sato H, Sugawara J, Ito S, Takahashi N
Abstract
Systemic lupus erythematosus (SLE) increases the risk of preterm birth and preeclampsia (PE). The flares of SLE during pregnancy or after delivery are also problematic. We have previously demonstrated that nicotinamide (NAM), a non-teratogenic amide of vitamin B3, reduces inflammation and oxidative stress and improves PE-like phenotype and pregnancy outcomes in the mouse models of PE. The present study aimed to establish a model to investigate the pregnancy outcomes and flares of SLE in pregnant mice with SLE and to examine whether NAM is beneficial to pregnant mice with SLE. We used pregnant and non-pregnant lupus-prone MRL/lpr mice treated with or without a Toll-like receptor (TLR) ligand lipopolysaccharide (LPS) because TLR4 signaling reportedly exacerbates SLE and pregnancy; MRL/+ mice were used as controls. Blood pressure (BP) and urinary albumin excretion were increased only in the pregnant MRL/lpr-LPS mice. LPS together with pregnancy exacerbated glomerulonephritis, and the most severe inflammation was observed in the kidneys of the pregnant MRL/lpr-LPS mice. The shortening of pregnancy periods, increase in fetal demise percentage, and reduction in fetal weight were observed only in the pregnant MRL/lpr-LPS mice. NAM improved BP and kidney injury, prolonged pregnancy periods, and improved fetal growth in the pregnant MRL/lpr-LPS mice. The results suggest that SLE patients are prone to develop poor pregnancy outcome, and likely develop severe nephropathy and kidney inflammation. NAM may be a novel therapeutic option that improves kidney injury and pregnancy outcomes, thereby benefiting pregnant patients with SLE.
PMID: 30739788 [PubMed – as supplied by publisher]
PubMed:30739788
Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome
https://www.sciencedirect.com/science/article/pii/S1567576918313286?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30738291?dopt=Abstract
Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome.
Int Immunopharmacol
Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome.
Int Immunopharmacol. 2019 Feb 06;69:213-216
Authors: Zhao J, Wang J, Zhou M, Li M, Li M, Tan H
Abstract
Despite rapid progress in the understanding of systemic lupus erythematosus (SLE), there is still an urgent need for novel and more effective interventions. Curcumin, a natural polyphenol compound, has been shown to be anti-inflammatory in various disorders. In this study, we investigated the potential therapeutic value of curcumin in SLE. Lupus-prone female MRL/lpr mice were treated with curcumin. The development and extent of nephritis were assessed by monitoring proteinuria and by histologic analysis. Serum anti-dsDNA levels were measured by enzyme-linked immunosorbent assay. Kidney samples were analyzed by Western blot. In vitro, mouse podocytes were used for investigation in the presence of mouse anti-dsDNA antibody-positive (anti-dsDNA+) serum. Curcumin treatment dramatically decreased proteinuria and renal inflammation. Serum anti-dsDNA levels and spleen size were also reduced by curcumin. In addition, curcumin reduced NLRP3 inflammasome activation in lupus-prone mice. In vitro, curcumin significantly inhibited anti-dsDNA+ serum induced expression of NLRP3 inflammasome in podocytes. Overall, these data demonstrate the potential use of curcumin in SLE treatment.
PMID: 30738291 [PubMed – as supplied by publisher]
PubMed:30738291
miR-152 Attenuates the Severity of Lupus Nephritis Through the Downregulation of Macrophage Migration Inhibitory Factor (MIF)-Induced Expression of COL1A1
These findings suggest that miR-152 may be a potential target for the treatment of LN.
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00158/full
https://www.ncbi.nlm.nih.gov/pubmed/30787934?dopt=Abstract
A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT02437890?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F23%2F2019&lupd_d=14
Condition : Lupus Erythematosus, Systemic
Interventions : Biological: ALX-0061; Biological: Placebo
Sponsor : Ablynx
Completed
A Phase II Study to Evaluate Safety and Efficacy of ALX-0061 in Subjects With Systemic Lupus Erythematosus
NCT02437890
Fri, 08 May 2015 12:00:00 EDT
>>> completed and results posted
Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients
https://clinicaltrials.gov/ct2/show/NCT03656562?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F23%2F2019&lupd_d=14
Condition : Systemic Lupus Erythematosus (SLE)
Interventions : Drug: VAY736; Drug: VAY736 Placebo; Drug: CFZ533; Drug: CFZ533 Placebo
Sponsor : Novartis Pharmaceuticals
Recruiting
Study the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients
NCT03656562
Mon, 03 Sep 2018 12:00:00 EDT
Epigenetically Altered T Cells Contribute to Lupus Flares
https://www.mdpi.com/2073-4409/8/2/127
https://www.ncbi.nlm.nih.gov/pubmed/30764520?dopt=Abstract
Epigenetically Altered T Cells Contribute to Lupus Flares.
Cells
Related Articles
Epigenetically Altered T Cells Contribute to Lupus Flares.
Cells. 2019 Feb 05;8(2):
Authors: Richardson B
Abstract
Lupus flares when genetically predisposed people encounter exogenous agents such as infections and sun exposure and drugs such as procainamide and hydralazine, but the mechanisms by which these agents trigger the flares has been unclear. Current evidence indicates that procainamide and hydralazine, as well as inflammation caused by the environmental agents, can cause overexpression of genes normally silenced by DNA methylation in CD4⁺ T cells, converting them into autoreactive, proinflammatory cytotoxic cells that are sufficient to cause lupus in mice, and similar cells are found in patients with active lupus. More recent studies demonstrate that these cells comprise a distinct CD4⁺ T cell subset, making it a therapeutic target for the treatment of lupus flares. Transcriptional analyses of this subset reveal proteins uniquely expressed by this subset, which may serve as therapeutic to deplete these cells, treating lupus flares.
PMID: 30764520 [PubMed]
PubMed:30764520
Researchers reveal how receptor TLR-9 protects against lupus
https://medicalxpress.com/news/2019-02-reveal-receptor-tlr-lupus.html
Researchers reveal how receptor TLR-9 protects against lupus
Neovacs to host KOL Meeting to discuss its therapeutic vaccine IFNalpha Kinoid for lupus treatment – February 11th Paris
https://globenewswire.com/news-release/2019/02/05/1710290/0/en/Neovacs-to-host-KOL-Meeting-to-discuss-its-therapeutic-vaccin-IFNalpha-Kinoid-for-lupus-treatment-February-11th-Paris.html
Neovacs to host KOL Meeting to discuss its therapeutic vaccin IFNalpha Kinoid for lupus treatment – February 11th Paris
>>> fixed typo in title (vaccin = french word for vaccine)
Drug-induced systemic lupus: revisiting the ever-changing spectrum of the disease using the WHO pharmacovigilance database
This study enables the identification of 118 drugs associated with DIL. The list of suspected drugs may prove useful to physicians when confronted with potential DIL cases.
https://ard.bmj.com/content/early/2019/02/03/annrheumdis-2018-214598
https://www.ncbi.nlm.nih.gov/pubmed/30793701?dopt=Abstract
Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis
https://clinicaltrials.gov/ct2/show/NCT03828071?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F21%2F2019&lupd_d=14
Condition : Lupus Nephritis
Intervention : Procedure: Autologous hematopoietic stem cell transplantation
Sponsor : Nanjing University School of Medicine
Completed
Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis
NCT03828071
Mon, 04 Feb 2019 12:00:00 EST
Tetra-arsenic tetra-sulfide Ameliorates Lupus Syndromes by Inhibiting IL-17 producing Double Negative T cells
https://onlinelibrary.wiley.com/doi/abs/10.1111/dth.12849
https://www.ncbi.nlm.nih.gov/pubmed/30707471?dopt=Abstract
Tetra-arsenic tetra-sulfide Ameliorates Lupus Syndromes by Inhibiting IL-17 producing Double Negative T cells.
Dermatol Ther
Tetra-arsenic tetra-sulfide Ameliorates Lupus Syndromes by Inhibiting IL-17 producing Double Negative T cells.
Dermatol Ther. 2019 Feb 01;:e12849
Authors: Zhao Y, Mu Z, Cai L, Liu X, Jun J, Zhang J
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra-arsenic tetra-sulfide (As4 S4 ), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus-prone mice treated with As4 S4 has showed improved monocytosis, decreased serum interleukin-6 (IL-6) and suppressed skin, liver and renal lesions with well-tolerance. In this study, we explored the effect and mechanism of As4 S4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As4 S4 treatment groups and dosed with As4 S4 or placebo for 8 weeks. We found that As4 S4 prevented the skin, renal and lung lesions of MRL/lpr mice. As4 S4 significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL-17, IL-10, and antinuclear antibodies (ANA) titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As4 S4 treated MRL/lpr mice. Taken together, As4 S4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL-17, which may be produced by DN T cells. As4 S4 may represent a new therapy for SLE. This article is protected by copyright. All rights reserved.
PMID: 30707471 [PubMed – as supplied by publisher]
PubMed:30707471
Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care
https://clinicaltrials.gov/ct2/show/NCT033712513o9
Study of BOS161721 in Systemic Lupus Erythematosus (SLE) Patients on a Background of Limited Standard of Care
Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-1820-3
https://www.ncbi.nlm.nih.gov/pubmed/30696480?dopt=Abstract
Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage.
Arthritis Res Ther
Related Articles
Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage.
Arthritis Res Ther. 2019 Jan 29;21(1):40
Authors: He S, Liu X, Lin Z, Liu Y, Gu L, Zhou H, Tang W, Zuo J
Abstract
BACKGROUND: Glomerulonephritis is one of the major complications and causes of death in systemic lupus erythematosus (SLE) and is characterized by glomerulosclerosis, interstitial fibrosis, and tubular atrophy, along with severe persistent proteinuria. DZ2002 is a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with potent therapeutic activity against lupus nephritis in mice. However, the molecular events underlying the renal protective effects of DZ2002 remained unclear. This study is designed to uncover the molecular mechanisms of DZ2002 on glomerulonephritis of lupus-prone mice.
METHODS: We conducted a twice-daily treatment of DZ2002 on the lupus-prone NZB/WF1 mice, and the progression of lupus nephritis and alteration of renal function were monitored. The LC-MS-based label-free quantitative (LFQ) proteomic approach was applied to analyze the kidney tissue samples from the normal C57BL/6 mice and the NZB/WF1 mice treated with DZ2002 or vehicle. KEGG pathway enrichment and direct protein-protein interaction (PPI) network analyses were used to map the pathways in which the significantly changed proteins (SCPs) are involved. The selected proteins from proteomic analysis were validated by Western blot analysis and immunohistochemistry in the kidney tissues.
RESULTS: The twice-daily regimen of DZ2002 administration significantly ameliorated the lupus nephritis and improved the renal function in NZB/WF1 mice. A total of 3275 proteins were quantified, of which 253 proteins were significantly changed across normal C57BL/6 mice and the NZB/WF1 mice treated with DZ2002 or vehicle. Pathway analysis revealed that 13 SCPs were involved in tight junction and focal adhesion process. Further protein expression validation demonstrated that DZ2002-treated NZB/WF1 mice exhibited downregulation of α-actinin-4 and integrin-linked kinase (ILK), as well as the restoration of β1-integrin activation in the kidney tissues compared with the vehicle-treated ones.
CONCLUSIONS: Our study demonstrated the first evidence for the molecular mechanism of SAHH inhibitor on glomerulonephritis in SLE via the modulation of α-actinin-4 expression and focal adhesion-associated signaling proteins in the kidney.
PMID: 30696480 [PubMed – in process]
PubMed:30696480
A Phase 2 Efficacy and Safety Study of Dapirolizumab Pegol (DZP) in Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT02804763?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F15%2F2019&lupd_d=14
Condition : Systemic Lupus Erythematosus (SLE)
Interventions : Drug: Placebo; Drug: Dapirolizumab pegol (DZP)
Sponsor : UCB Biopharma S.P.R.L.
Completed
A Phase 2 Efficacy and Safety Study of Dapirolizumab Pegol (DZP) in Systemic Lupus Erythematosus
NCT02804763
Fri, 17 Jun 2016 12:00:00 EDT
>>> Updated January 29, 2019 >>> study status changed from active, not recruiting to completed
‘Rogue’ clones linked to Lupus disease
‘Rogue’ clones linked to Lupus disease
Rituxan Fails to Treat Moderate to Severe SLE without Kidney Involvement, Trial Reanalysis Confirms
– https://lupusnewstoday.com/2019/01/25/rituxan-fails-to-treat-moderate-to-severe-sle-without-kidney-involvement-trial-reanalysis-confirms/
Rituxan Fails to Treat Moderate to Severe SLE without Kidney Involvement, Trial Reanalysis Confirms
January 25, 2019
study: https://ard.bmj.com/content/early/2019/01/04/annrheumdis-2018-214833
A Study to Evaluate VIB7734 in Participants With Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Sjogren’s Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis
https://clinicaltrials.gov/ct2/show/NCT03817424?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F11%2F2019&lupd_d=14
Conditions : Systemic Lupus Erythematosus; Cutaneous Lupus Erythematosus; Sjogren’s Syndrome; Systemic Sclerosis; Polymyositis; Dermatomyositis
Interventions : Drug: VIB7734; Drug: Placebo
Sponsor : Viela Bio
Recruiting
A Study to Evaluate VIB7734 in Participants With Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Sjogren’s Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis
NCT03817424
Fri, 25 Jan 2019 12:00:00 EST
Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus
https://www.sciencedirect.com/science/article/pii/S0142961219300559?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30703743?dopt=Abstract
Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus.
Biomaterials
Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus.
Biomaterials. 2019 Jan 23;197:380-392
Authors: Xu N, Li J, Gao Y, Zhou N, Ma Q, Wu M, Zhang Y, Sun X, Xie J, Shen G, Yang M, Tu Q, Xu X, Zhu J, Tao J
Abstract
Systemic lupus erythematosus (SLE) constitutes an autoimmune disease characterized by the breakdown of tolerance to self-antigens, sustained production of pathogenic autoantibodies, and damage to multiple organs and tissues. Nanoparticle (NP)-based therapeutics have demonstrated efficacy in attenuating the progression of SLE. However, investigations of nano-drugs that address the crucial initiating factor in the pathogenesis of SLE; e.g., inefficient clearance of apoptotic cells by phagocytes and consequent accumulation of self-antigens, have seldom been reported. Here, an apoptotic cell-mimicking gold nanocage (AuNC)-based nano drug carrier capable of correcting the impaired clearance of apoptotic cells in SLE was rationally designed and generated by conjugating phosphatidylserine (PS) on the surface of liposome-coated AuNCs for liver X receptor (LXR) agonist T0901317 delivery. Notably, PS-lipos-AuNC@T0901317 could efficiently enhance apoptotic cell clearance by elevating the expression of Mer, one of the pivotal phagocytosis-associated receptors on macrophages, resulting in decreased production of anti-dsDNA autoantibodies, reduced inflammatory response, and alleviation of kidney damage in lupus model mice. Additionally, PS-lipos-AuNC could be tracked by photoacoustic imaging for nano drug carrier biodistribution. By addressing the crucial pathogenic factor of SLE, the NP-based delivery system in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.
PMID: 30703743 [PubMed – as supplied by publisher]
PubMed:30703743
Targeted Treatment of TREX1 Chilblain Lupus and Other Interferonopathies-Taming T REX
https://jamanetwork.com/journals/jamadermatology/article-abstract/2720743
https://www.ncbi.nlm.nih.gov/pubmed/30673073?dopt=Abstract
Targeted Treatment of TREX1 Chilblain Lupus and Other Interferonopathies-Taming T REX.
JAMA Dermatol
Targeted Treatment of TREX1 Chilblain Lupus and Other Interferonopathies-Taming T REX.
JAMA Dermatol. 2019 Jan 23;:
Authors: Damsky W, King BA
PMID: 30673073 [PubMed – as supplied by publisher]
PubMed:30673073
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation
https://jamanetwork.com/journals/jamadermatology/fullarticle/2720741
https://www.ncbi.nlm.nih.gov/pubmed/30673078?dopt=Abstract
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation.
JAMA Dermatol
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation.
JAMA Dermatol. 2019 Jan 23;:
Authors: Zimmermann N, Wolf C, Schwenke R, Lüth A, Schmidt F, Engel K, Lee-Kirsch MA, Günther C
Abstract
Importance: Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous lupus erythematosus that in most cases is caused by mutations in the 3 prime repair exonuclease 1 (TREX1). Familial chilblain lupus presents in early childhood with cold-induced painful erythematous infiltrates leading to mutilation and is associated with systemic involvement illustrated by an elevated type I interferon (IFN) signature in the skin and blood. Effective treatment is currently not available.
Objectives: To evaluate the clinical response to the Janus kinase inhibitor baricitinib in familial chilblain lupus and assess the effect of cold on patient fibroblasts.
Design, Setting, and Participants: In this case series, 3 patients with familial chilblain lupus due to TREX1 mutation underwent treatment with baricitinib for 3 months.
Interventions: Doses of baricitinib, 4 mg, were administered daily for 3 months.
Main Outcomes and Measures: Reduction of cutaneous lupus lesions was measured by the revised cutaneous lupus area and severity index, pain due to skin and joint involvement was assessed by visual analog scale, type I IFN signature in blood was determined by polymerase chain reaction, and the in vitro response of fibroblasts to cold exposure was analyzed.
Results: All 3 patients (2 women and 1 man; mean [SD] age, 51 [24] years) showed a significant improvement of cutaneous lupus lesions with suppression of systemic type I IFN activation. One patient had a complete remission regarding pain and, in 2 patients, pain associated with joint inflammation was partially reduced. No severe adverse reactions were reported. Exposure of patient fibroblasts to cold induced a stress response and enhanced senescence along with induction of IFN-stimulated gene in vitro.
Conclusions and Relevance: These findings demonstrate the therapeutic efficacy of Janus kinase inhibition in a monogenic form of lupus among 3 patients and provide mechanistic insight into the process of disease exacerbation by cold in TREX1-deficient cells. This finding may be relevant to other type I IFN-mediated disorders and implicates Janus kinase inhibition as a potential therapeutic option also for multifactorial cutaneous lupus erythematosus.
PMID: 30673078 [PubMed – as supplied by publisher]
PubMed:30673078
Safety and Tolerability Study Of PF-06835375 In Subjects With Seropositive Systemic Lupus Erythematosus Or Rheumatoid Arthritis
https://clinicaltrials.gov/ct2/show/NCT03334851?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F09%2F2019&lupd_d=14
Conditions : Systemic Lupus Erythematosus; Rheumatoid Arthritis
Interventions : Drug: PF-06835375; Drug: Placebo
Sponsor : Pfizer
Recruiting
Safety and Tolerability Study Of PF-06835375 In Subjects With Seropositive Systemic Lupus Erythematosus Or Rheumatoid Arthritis
NCT03334851
Tue, 07 Nov 2017 12:00:00 EST
PAM3 supports the generation of M2-like macrophages from lupus patient monocytes and improves disease outcome in murine lupus
https://www.sciencedirect.com/science/article/pii/S0896841118306644?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30679006?dopt=Abstract
PAM3 supports the generation of M2-like macrophages from lupus patient monocytes and improves disease outcome in murine lupus.
J Autoimmun
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PAM3 supports the generation of M2-like macrophages from lupus patient monocytes and improves disease outcome in murine lupus.
J Autoimmun. 2019 Jan 21;:
Authors: Horuluoglu B, Bayik D, Kayraklioglu N, Goguet E, Kaplan MJ, Klinman DM
Abstract
Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed that the TLR2/1 agonist PAM3CSK4 (PAM3) could stimulate normal human monocytes to preferentially differentiate into immunosuppressive M2-like rather than inflammatory M1-like macrophages. This raised the possibility of PAM3 being used to normalize the M1:M2 ratio in SLE. Consistent with that possibility, monocytes from lupus patients differentiated into M2-like macrophages when treated with PAM3 in vitro. Furthermore, lupus-prone NZB x NZW F1 mice responded similarly to weekly PAM3 treatment. Normalization of the M2 macrophage frequency was associated with delayed disease progression, decreased autoantibody and inflammatory cytokine synthesis, reduced proteinuria and prolonged survival in NZB x NZW F1 mice. The ability of PAM3 to bias monocyte differentiation in favor of immunosuppressive macrophages may represent a novel approach to the therapy of SLE.
PMID: 30679006 [PubMed – as supplied by publisher]
PubMed:30679006
An Investigational Study to Evaluate BMS-986165 in Patients With Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT03252587
An Investigational Study to Evaluate BMS-986165 in Patients With Systemic Lupus Erythematosus
A Study of Baricitinib (LY3009104) in Participants With Systemic Lupus Erythematosus (BRAVE I)
https://clinicaltrials.gov/ct2/show/NCT03616912
A Study of Baricitinib (LY3009104) in Participants With Systemic Lupus Erythematosus (BRAVE I)
A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (BRAVE II)
https://clinicaltrials.gov/ct2/show/NCT03616964
A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (BRAVE II)
JBT-101 in Systemic Lupus Erythematosus (SLE)
https://clinicaltrials.gov/ct2/show/NCT03093402?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F04%2F2019&lupd_d=14
Conditions : Systemic Lupus Erythematosus; SLE; Lupus
Interventions : Drug: JBT-101; Drug: Placebo
Sponsors : National Institute of Allergy and Infectious Diseases (NIAID); Corbus Pharmaceuticals Inc.; Autoimmunity Centers of Excellence
Recruiting
JBT-101 in Systemic Lupus Erythematosus (SLE)
NCT03093402
Tue, 28 Mar 2017 12:00:00 EDT
Current challenges in the development of new treatments for lupus
https://ard.bmj.com/content/early/2019/01/11/annrheumdis-2018-214530
urrent challenges in the development of new treatments for lupus
Safety and Efficacy of AMG 592 in Subjects With Active Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT03451422?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F03%2F2019&lupd_d=14
Condition : Systemic Lupus Erythematosus
Interventions : Drug: AMG 592; Drug: Placebo
Sponsor : Amgen
Recruiting
Safety and Efficacy of AMG 592 in Subjects With Active Systemic Lupus Erythematosus
NCT03451422
Thu, 01 Mar 2018 12:00:00 EST
Flinders team claims breakthrough in Lupus research
https://www.itwire.com/health/85739-flinders-team-claims-breakthrough-in-lupus-research.html
Flinders team claims breakthrough in Lupus research
Phase 2 Trial of Mesenchymal Stem Cells in Systemic Lupus Erythematosus (MiSLE)
https://clinicaltrials.gov/ct2/show/NCT02633163
Phase 2 Trial of Mesenchymal Stem Cells in Systemic Lupus Erythematosus (MiSLE)
Role of circulating T follicular helper subsets and T follicular helper effector memory cells in systemic lupus erythematosus
https://www.ncbi.nlm.nih.gov/pubmed/30669756?dopt=Abstract
[Role of circulating T follicular helper subsets and T follicular helper effector memory cells in systemic lupus erythematosus].Zhonghua Yi Xue Za Zhi
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[Role of circulating T follicular helper subsets and T follicular helper effector memory cells in systemic lupus erythematosus].Zhonghua Yi Xue Za Zhi. 2019 Jan 15;99(3):164-168
Authors: Liang YC, Yao Y, Zhang RJ, Shao M, Sun XL, Shi GX, Gao C, Yu D, He J
Abstract
Objective: To investigate the role of T follicular helper (Tfh) subsets and T follicular helper effector memory (Tfhem) cells in circulation of patients with systemic lupus erythematosus (SLE), and explore their roles in SLE disease activity index as biomarkers. Methods: This study enrolled 64 patients with SLE and 15 healthy controls. In peripheral blood from patients with SLE and health controls, the percentage of Tfhem (CD3(+)CD4(+)CD45RA(-)CXCR5(+)CCR7(low)PD-1(high)) cells, Tfh (CD3(+)CD4(+)CD127(high)CD25(l)ow CD45RA(-)CXCR5(+)) subset: Tfh1 (CXCR3(+)CCR6(-)Tfh), Tfh2 (CXCR3(-)CCR6(+) Tfh), Tfh17 (CXCR3(-)CCR6(+) Tfh), were detected by flow cytometry. The correlations of Tfhem/Tfh subsets with clinical indicators which we collected were analyzed. Results: The percentage of Tfhem was significantly increased in SLE patients compare to health controls (1.40±1.12 vs 0.51±0.24, P<0.000 1), and it was also correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P=0.015 3) and anti-dsDNA antibody (P=0.003 1), but not with complement C3 (C3), complement C4 (C4), erythrocyte sedimentation rate (ESR), and C reaction protein (CRP). In addition, the percentage of Tfh2, but not Tfh1 or Tfh17, was significantly increased in SLE patients compare to health controls (3.83±2.74 vs 2.18±1.07, P=0.000 4). As compared to anti-dsDNA antibody<25 group, the percentage of Tfh2 in anti-dsDNA antibody>25 group was increased with no significant statistical difference (4.33±3.20 vs 3.70±1.070, P=0.069 6). Conclusion: Our investigation show that Tfhem is associated with SLEDAI and it is a valuable evaluation biomarker for disease process and treatment. Meanwhile Tfhem is also associated with anti-dsDNA antibody, and it plays an important role in autoantibody production in SLE pathogenesis. Tfhem may be a good therapeutic target in SLE. For the meantime, the percentage of Tfh2 is significantly increased in SLE patients, and it had certain correlation with anti-dsDNA antibody, it might be involved in the development of SLE.
PMID: 30669756 [PubMed – in process]
PubMed:30669756
IFNalpha Kinoid Continues to be Studied for Treatment of Systemic Lupus Erythematosus
https://www.lupus.org/news/ifnalpha-kinoid-continues-to-be-studied-for-treatment-of-systemic-lupus-erythematosus
IFNalpha Kinoid Continues to be Studied for Treatment of Systemic Lupus Erythematosus
A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT03161483
A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus
Approved Asthma Therapy Omalizumab Reduces SLE Disease Activity, Phase 1b Trial Finds
Approved Asthma Therapy Omalizumab Reduces SLE Disease Activity, Phase 1b Trial Finds
Approved Asthma Therapy Omalizumab Reduces SLE Disease Activity, Phase 1b Trial Finds
Asthma Drug Explored in SLE
https://www.medpagetoday.com/rheumatology/lupus/77416
Asthma Drug Explored in SLE
– Anti-IgE antibody promising as add-on therapy in phase 1b study
Lupus Research Alliance Announces Translational Research Grants to Speed Development of New Treatments
https://www.prnewswire.com/news-releases/lupus-research-alliance-announces-translational-research-grants-to-speed-development-of-new-treatments-300776585.html
Lupus Research Alliance Announces Translational Research Grants to Speed Development of New Treatments
NEW YORK, Jan. 10, 2019 /PRNewswire/ — Can “borrowed” drugs for treating other diseases protect the skin in patients with lupus? Can researchers coax the body to weed out harmful immune cells that drive tissue destruction in lupus? Those are just two of the innovative approaches for lupus therapies recognized by the Lupus Research Alliance with the latest round of its Target Identification in Lupus (TIL) grants. Seven outstanding scientists from across the United States will receive awards worth up to $600,000 for research projects designed to test promising strategies for treating lupus.
Impact of belimumab on patient-reported outcomes in systemic lupus erythematosus: review of clinical studies
https://www.dovepress.com/impact-of-belimumab-on-patient-reported-outcomes-in-systemic-lupus-ery-peer-reviewed-article-PROM
https://www.ncbi.nlm.nih.gov/pubmed/30666173?dopt=Abstract
Impact of belimumab on patient-reported outcomes in systemic lupus erythematosus: review of clinical studies.
Patient Relat Outcome Meas
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Impact of belimumab on patient-reported outcomes in systemic lupus erythematosus: review of clinical studies.
Patient Relat Outcome Meas. 2019;10:1-7
Authors: Bangert E, Wakani L, Merchant M, Strand V, Touma Z
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune, multisystem rheumatic disease with significant impact on health-related quality of life (HRQoL). Patient-reported outcomes (PROs) provide valuable data on patient perceptions across a variety of domains, such as HRQoL, pain, fatigue, and depression. The measurement and results of PROs with respect to HRQoL in randomized controlled trials (RCTs) on belimumab (B-lymphocyte stimulator inhibitor) in SLE are reviewed here, including BLISS-52 and BLISS-76, as well as publications related to belimumab trials that included HRQoL data. Other trials that evaluated belimumab did not include HRQoL data and were therefore not included in the analysis. The BLISS-52 and BLISS-76 RCTs met their primary endpoints and demonstrated improvements in PROs, measured by the 36-item Short Form Health Survey, EuroQol 5 Dimensions, and Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Belimumab was shown overall to improve PROs in adult autoantibody-positive lupus patients.
PMID: 30666173 [PubMed]
PubMed:30666173
BI 705564 in Patients With Systemic Lupus Erythematosus (SLE)
https://clinicaltrials.gov/ct2/show/NCT03771885?type=Intr&cond=Lupus&phase=012345&lupd_s=01%2F02%2F2019&lupd_d=14
Condition : Lupus Erythematosus, Systemic
Interventions : Drug: BI 705564; Drug: Placebo
Sponsor : Boehringer Ingelheim
Not yet recruiting
BI 705564 in Patients With Systemic Lupus Erythematosus (SLE)
NCT03771885
Tue, 11 Dec 2018 12:00:00 EST
>>> updated jan 8, 2019
Idorsia initiates a multiple-dose efficacy and safety study with cenerimod for the treatment of systemic lupus erythematosus
https://globenewswire.com/news-release/2019/01/07/1680934/0/en/Idorsia-initiates-a-multiple-dose-efficacy-and-safety-study-with-cenerimod-for-the-treatment-of-systemic-lupus-erythematosus.html
Gene-function studies in systemic lupus erythematosus
https://journals.lww.com/co-rheumatology/Abstract/2019/03000/Gene_function_studies_in_systemic_lupus.14.aspx
https://www.ncbi.nlm.nih.gov/pubmed/30540578
Gene-function studies in systemic lupus erythematosus
Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
https://clinicaltrials.gov/ct2/show/NCT03742037
Efficacy and Safety of Four Doses of Cenerimod Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
ClinicalTrials.gov Identifier: NCT03742037
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : December 24, 2018Sponsor:
Idorsia Pharmaceuticals Ltd.
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.
Brief Summary:
The purpose of the study is to assess the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with systemic lupus erythematosus (SLE).
Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus
Drug: Cenerimod 0.5 mg
Drug: Cenerimod 1 mg
Drug: Cenerimod 2 mg
Drug: Cenerimod 4 mg
Drug: Placebo
Phase 2
Detailed Description:
This is a Phase 2b, multicenter, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).
Approximately 500 adult subjects with SLE will be randomized in a 1:1:1:1:1 ratio to placebo, 0.5, 1, 2, or 4 mg o.d. of cenerimod, in addition to background SLE therapy.
Study Design
Go to sections
Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Cenerimod in Subjects With Moderate to Severe Systemic Lupus Erythematosus (SLE)
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : May 17, 2021
Estimated Study Completion Date : September 15, 2021
FDA Grants Fast Track Status to Drug Being Studied for Lupus Treatment
https://www.lupus.org/news/fda-grants-fast-track-status-to-drug-being-studied-for-lupus-treatment
FDA Grants Fast Track Status to Drug Being Studied for Lupus Treatment
FDA grants fast track status to baricitinib development for SLE
https://www.healio.com/rheumatology/lupus/news/online/%7Bed065fab-9215-4681-ab99-4070a986037a%7D/fda-grants-fast-track-status-to-baricitinib-development-for-sle
Neovacs and Centurion Pharma continue their collaboration in Lupus based on the results of the Phase IIb trial with IFNalpha Kinoid
https://globenewswire.com/news-release/2018/12/11/1664824/0/en/Neovacs-and-Centurion-Pharma-continue-their-collaboration-in-Lupus-based-on-the-results-of-the-Phase-IIb-trial-with-IFNalpha-Kinoid.html
Neovacs and Centurion Pharma continue their collaboration in Lupus based on the results of the Phase IIb trial with IFNalpha Kinoid
Potential New Lupus Treatment Outperforms Hydroxychloroquine in Animal Study
Potential New Lupus Treatment Outperforms Hydroxychloroquine in Animal Study
Potential New Lupus Treatment Outperforms Hydroxychloroquine in Animal Study
Stem Cell Treatment Seen to Benefit Lupus Patients in Phase 1 Trial, New Study Opening
Stem Cell Treatment Seen to Benefit Lupus Patients in Phase 1 Trial, New Study Opening
Stem Cell Treatment Seen to Benefit Lupus Patients in Phase 1 Trial, New Study Opening
Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis
https://journals.sagepub.com/doi/10.1177/0961203318804922
Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis
Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets
https://www.ncbi.nlm.nih.gov/pubmed/29680223?dopt=Abstract
Related Articles
Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets.
Cancer Lett. 2018 08 01;428:90-103
Authors: Long H, Wang X, Chen Y, Wang L, Zhao M, Lu Q
Abstract
MicroRNAs (miRNAs) are small, single-stranded, endogenous non-coding RNAs that repress the expression of target genes via post-transcriptional mechanisms. Due to their broad regulatory effects, the precisely regulated, spatial-specific and temporal-specific expression of miRNAs is fundamentally important to various biological processes including the immune homeostasis and normal function of both innate and adaptive immune response. Aberrance of miRNAs is implicated in the development of various human diseases, especially cancers. Increasing evidence has revealed a dysregulated expression pattern of miRNAs in autoimmune diseases, among which many play key roles in the pathogenesis. In this review we summarize these findings on miRNA dysregulation implicated in autoimmune diseases, focusing on four representative systemic autoimmune diseases, i.e. systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and dermatomyositis. The causes of the dysregulation of miRNA expression in autoimmune diseases may include genetic and epigenetic variants, and various environmental factors. Further understanding of miRNA dysregulation and its mechanisms during the development of different autoimmune diseases holds enormous potential to bring about novel therapeutic targets or strategies for these complex human disorders, as well as novel circulating or exosomal miRNA biomarkers.
PMID: 29680223 [PubMed – indexed for MEDLINE]
PubMed:29680223
Scientific and Technology Breakthroughs Show Promise for Lupus and Other Immunologic Diseases
https://www.prnewswire.com/news-releases/scientific-and-technology-breakthroughs-show-promise-for-lupus-and-other-immunologic-diseases-300681552.html
Scientific and Technology Breakthroughs Show Promise for Lupus and Other Immunologic Diseases
Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery
https://www.tandfonline.com/doi/abs/10.1080/17460441.2018.1480718?journalCode=iedc20
https://www.ncbi.nlm.nih.gov/pubmed/29863906?dopt=Abstract
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Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery.
Expert Opin Drug Discov. 2018 08;13(8):765-777
Authors: Li Y, Wu T
Abstract
INTRODUCTION: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a high risk of morbidity and mortality; however, there is no cure and the current medications are far from optimal in addressing efficacy and safety concerns. Over the past decade, various emerging technologies have been used in the search for novel drug targets of SLE which have resulted in numerous promising data. However, the systematic review and careful digestion of this information have been lacking. Areas covered: In this review, the authors summarize promising biomarkers and drug targets which have been identified via various multiplexing and high-throughput proteomic strategies. The authors also introduce emerging technologies which are hopeful to be used for the discovery of novel biomarkers and therapeutic targets of SLE in the near future. Expert opinion: Emerging proteomic technologies and genome-wide association studies (GWAS) have been the new driving forces in the discovery of novel biomarkers and promising therapeutic targets of SLE. Careful validation of these potential targets in lupus mouse models and clinical trials are urgently needed so that the next generation of target-specific medications can be developed for SLE patients.
PMID: 29863906 [PubMed – indexed for MEDLINE]
PubMed:29863906
Inhibition of Cyclic GMP‐AMP Synthase Using a Novel Antimalarial Drug Derivative in Trex1‐Deficient Mice
https://onlinelibrary.wiley.com/doi/10.1002/art.40559
Inhibition of Cyclic GMP‐AMP Synthase Using a Novel Antimalarial Drug Derivative in Trex1‐Deficient Mice
Jie An PhD Joshua J. Woodward PhD Weinan Lai MD Mark Minie PhD Xizhang Sun PhD Lena Tanaka MS Jessica M. Snyder DVM Tomikazu Sasaki PhD Keith B. Elkon MD
First published: 21 May 2018 https://doi.org/10.1002/art.40559
Supported by the Life Sciences Discovery Fund (grant 15834191), the Alliance for Lupus Research (Rare Disease Foundation Microgrant), and the University of Washington Innovation Fund. Research in Dr. Woodward’s laboratory is supported by the Pew Charitable Trust (Biomedical Scholarship). Dr. Lai’s work was supported by the Nanfang Hospital Science Foundation of China (grant 2014C008) and the Natural Science Foundation of Guangdong Province (grant 2017A030313508).
Drs. An, Woodward, Minie, Sasaki, and Elkon have a patent pending on the compounds X5–X7 described in this study.
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Abstract
Objective
Type I interferon (IFN) is strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE) as well as rare monogenic interferonopathies such as Aicardi‐Goutières syndrome (AGS), a disease attributed to mutations in the DNA exonuclease TREX1. The DNA‐activated type I IFN pathway cyclic GMP‐AMP (cGAMP) synthase (cGAS) is linked to subsets of AGS and lupus. This study was undertaken to identify inhibitors of the DNA–cGAS interaction, and to test the lead candidate drug, X6, in a mouse model of AGS.
Methods
Trex1−/− mice were treated orally from birth with either X6 or hydroxychloroquine (HCQ) for 8 weeks. Expression of IFN‐stimulated genes (ISGs) was quantified by quantitative polymerase chain reaction. Multiple reaction monitoring by ultra‐performance liquid chromatography coupled with tandem mass spectrometry was used to quantify the production of cGAMP and X6 drug concentrations in the serum and heart tissue of Trex1−/− mice.
Results
On the basis of the efficacy‐to‐toxicity ratio established in vitro, drug X6 was selected as the lead candidate for treatment of Trex1−/− mice. X6 was significantly more effective than HCQ in attenuating ISG expression in mouse spleens (P < 0.01 for Isg15 and Isg20) and hearts (P < 0.05 for Isg15, Mx1, and Ifnb, and P < 0.01 for Cxcl10), and in reducing the production of cGAMP in mouse heart tissue (P < 0.05), thus demonstrating target engagement by the X6 compound. Of note, X6 was also more effective than HCQ in reducing ISG expression in vitro (P < 0.05 for IFI27 and MX1, and P < 0.01 for IFI44L and PKR) in human peripheral blood mononuclear cells from patients with SLE.
Conclusion
This study demonstrates that X6 is superior to HCQ for the treatment of an experimental autoimmune myocarditis mediated in vivo by the cGAS/stimulator of IFN genes (cGAS/STING) pathway. The findings suggest that drug X6 could be developed as a novel treatment for AGS and/or lupus to inhibit activation of the cGAS/STING pathway.
Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus
https://www.ncbi.nlm.nih.gov/pubmed/30014641?dopt=Abstract
[The Study of Protective Effect of Paeoniflorin on Lung Injury in MRL/lpr Mice].Sichuan Da Xue Xue Bao Yi Xue Ban
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[The Study of Protective Effect of Paeoniflorin on Lung Injury in MRL/lpr Mice].Sichuan Da Xue Xue Bao Yi Xue Ban. 2018 May;49(3):394-398
Authors: Xie CH, Li ZJ, Chen LJ, Zhao P, Zhang JJ, Bai SW, Shen T, He WX, Wang YY
Abstract
OBJECTIVE: To investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model.
METHODS: Ten wild type mice and 40 MRL/lpr mice were used in this study. MRL/lpr mice were randomly assigned to MRL/lpr group,MRL/lpr + dexamethasone (1.5 mg/kg) group,MRL/lpr + paeoniflorin (20 mg/kg) group,and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde (MDA) , superoxide dismutase (SOD) ,catalase (CAT) ,glutathione peroxidase (GSH-Px) in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K),phospho-serine-threonine kinase B(P-Akt) ,phospho-nuclear factor kappa B (P-NF-κB),phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot.
RESULTS: Paeoniflorin decreased serum level of MDA and increased the levels of SOD,CAT,GSH-PX,and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K,P-Akt,P-NF-κBp65,and P-IκBα in the lung tissue of MRL/lpr mice.
CONCLUSION: Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.
PMID: 30014641 [PubMed – indexed for MEDLINE]
PubMed:30014641
Injectible drug shown to be effective against lupus in clinical trial
https://www.upi.com/Injectible-drug-shown-to-be-effective-against-lupus-in-clinical-trial/7941524247079/
Injectible drug shown to be effective against lupus in clinical trial
Lupus treatment generates positive results in Phase III clinical trial
https://www.sciencedaily.com/releases/2018/04/180420122847.htm
Lupus treatment generates positive results in Phase III clinical trial
Nrf2 as a therapeutic target for rheumatic diseases
https://www.sciencedirect.com/science/article/abs/pii/S0006295218301539?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/29660314?dopt=Abstract
Nrf2 as a therapeutic target for rheumatic diseases.
Biochem Pharmacol
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Nrf2 as a therapeutic target for rheumatic diseases.
Biochem Pharmacol. 2018 06;152:338-346
Authors: Ferrándiz ML, Nacher-Juan J, Alcaraz MJ
Abstract
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a master regulator of cellular protective processes. Rheumatic diseases are chronic conditions characterized by inflammation, pain, tissue damage and limitations in function. Main examples are rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis and osteoporosis. Their high prevalence constitutes a major health problem with an important social and economic impact. A wide range of evidence indicates that Nrf2 may control different mechanisms involved in the physiopathology of rheumatic conditions. Therefore, the appropriate expression and balance of Nrf2 is necessary for regulation of oxidative stress, inflammation, immune responses, and cartilage and bone metabolism. Numerous studies have demonstrated that Nrf2 deficiency aggravates the disease in experimental models while Nrf2 activation results in immunoregulatory and anti-inflammatory effects. These reports reinforce the increasing interest in the pharmacologic regulation of Nrf2 and its potential applications. Nevertheless, a majority of Nrf2 inducers are electrophilic molecules which may present off-target effects. In recent years, novel strategies have been sought to modulate the Nrf2 pathway which has emerged as a therapeutic target in rheumatic conditions.
PMID: 29660314 [PubMed – indexed for MEDLINE]
PubMed:29660314
AMG 557 showed safety and potential efficacy in patients with SLE
https://onlinelibrary.wiley.com/doi/full/10.1002/art.40479
https://www.ncbi.nlm.nih.gov/pubmed/29513931?dopt=Abstract
Related Articles
Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis.
Arthritis Rheumatol. 2018 07;70(7):1071-1076
Authors: Cheng LE, Amoura Z, Cheah B, Hiepe F, Sullivan BA, Zhou L, Arnold GE, Tsuji WH, Merrill JT, Chung JB
Abstract
OBJECTIVE: To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis.
METHODS: In this phase Ib, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1-letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).
RESULTS: The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4-point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (-36.3% versus -24.7%) and the SLEDAI score (-47.8% versus -10.7%) and in tender (-22.8% versus -13.5%) and swollen (-62.1% versus -7.8%) joint counts on day 169.
CONCLUSION: AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.
PMID: 29513931 [PubMed – indexed for MEDLINE]
PubMed:29513931
A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus
https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(18)30055-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671118300559%3Fshowall%3Dtrue
https://www.ncbi.nlm.nih.gov/pubmed/29478901?dopt=Abstract
A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus.
Stem Cell Reports
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A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus.
Stem Cell Reports. 2018 03 13;10(3):933-941
Authors: Wang D, Zhang H, Liang J, Wang H, Hua B, Feng X, Gilkeson GS, Farge D, Shi S, Sun L
Abstract
Allogeneic mesenchymal stem/stromal cells (MSCs) have been widely studied as an alternative cell source for regenerative medicine. Here, we report a long-term follow-up study of allogeneic bone marrow and/or umbilical cord MSC transplantation (MSCT) in severe and drug-refractory systemic lupus erythematosus (SLE) patients. Eighty-one patients were enrolled, and the 5-year overall survival rate was 84% (68/81) after MSCT. At 5-year follow-up, 27% of patients (22/81) were in complete clinical remission and another 7% (6/81) were in partial clinical remission, with a 5-year disease remission rate of 34% (28/81). In total, 37 patients had achieved clinical remission and then 9 patients subsequently relapsed, with 5-year overall rate of relapse of 24% (9/37). SLE Disease Activity Index scores, serum albumin, complement C3, peripheral white blood cell, and platelet numbers, as well as proteinuria levels, continued to improve during the follow-up. Our results demonstrated that allogeneic MSCT is safe and resulted in long-term clinical remission in SLE patients.
PMID: 29478901 [PubMed – indexed for MEDLINE]
PubMed:29478901
CXCR4-CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice
https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.201747023
https://www.ncbi.nlm.nih.gov/pubmed/29427452?dopt=Abstract
CXCR4-CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice.
Eur J Immunol
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CXCR4-CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice.
Eur J Immunol. 2018 06;48(6):1020-1029
Authors: Cheng Q, Khodadadi L, Taddeo A, Klotsche J, F Hoyer B, Radbruch A, Hiepe F
Abstract
Antibody-secreting cells (ASCs), including short-lived plasmablasts and long-lived memory plasma cells (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory to conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal cells expressing C-X-C motif chemokine-12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated the effects of CXCL12 and its ligand CXCR4 (C-X-C chemokine receptor 4) on ASCs in lupus mice (NZB/W). Fewer adoptively transferred splenic ASCs were retrieved from the bone marrow of recipient immunodeficient Rag1-/- mice when the ASCs were pretreated with the CXCR4 blocker AMD3100. CXCR4 blockade also significantly reduced anti-OVA ASCs in the bone marrow after secondary immunization with OVA. In this study, AMD3100 efficiently depleted ASCs, including LLPCs. After two weeks, it decreased the total number of ASCs in the spleen and bone marrow by more than 60%. Combination with the proteasome inhibitor bortezomib significantly enhanced the depletion effect of AMD3100. Continuous long-term (five-month) CXCR4 blockade with AMD3100 after effective short-term LLPCs depletion kept the number of LLPCs in the bone marrow low, delayed proteinuria development and prolonged the survival of the mice. These findings identify the CXCR4-CXCL12 axis as a potential therapeutic target likely due to its importance for ASC homing and survival.
PMID: 29427452 [PubMed – indexed for MEDLINE]
PubMed:29427452
Natural Killer (NK) cells could be an important future therapeutic target for SLE
https://www.ncbi.nlm.nih.gov/pubmed/29058308?dopt=Abstract
https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13073
Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus.
Clin Exp Immunol
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Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus.
Clin Exp Immunol. 2018 03;191(3):288-300
Authors: Cruz-González DJ, Gómez-Martin D, Layseca-Espinosa E, Baranda L, Abud-Mendoza C, Alcocer-Varela J, González-Amaro R, Monsiváis-Urenda AE
Abstract
Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3- CD56+ ) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c+ NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2)+ , CD86+ and CD134+ NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE patients when compared with controls. We have identified an expanded new subset of NK cells in SLE patients. This is the first study, to our knowledge, which demonstrates that NK cells in SLE patients have an altered phenotype with a high expression of receptors characteristic of dendritic cells. Our results suggest that the impairment in the regulatory function of NK cells, together with the increased number of DC-like NK cells, could play an important role in the development of SLE and highlight the importance of NK cells as a future therapeutic target.
PMID: 29058308 [PubMed – indexed for MEDLINE]
PubMed:29058308
New insights into the role of renal resident cells in the pathogenesis of lupus nephritis
http://kjim.org/journal/view.php?doi=10.3904/kjim.2017.383
https://www.ncbi.nlm.nih.gov/pubmed/29320847?dopt=Abstract
Related Articles
New insights into the role of renal resident cells in the pathogenesis of lupus nephritis.
Korean J Intern Med. 2018 03;33(2):284-289
Authors: Kwok SK, Tsokos GC
Abstract
Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. The immunopathogenesis of SLE is complex and most clinical trials of biologics targeting immune cells or their mediators have failed to show efficacy in SLE patients. It has therefore become increasingly clear that additional, local factors give rise to the inflammation and organ damage. In this review, we describe recent advances in the role of renal resident cells, including podocytes, mesangial cells, and epithelial cells, in the pathogenesis of lupus nephritis.
PMID: 29320847 [PubMed – indexed for MEDLINE]
PubMed:29320847
SLE: Systemic lupus erythematosus discussion – Reddit
https://www.reddit.com/r/lupus/
SLE: Systemic lupus erythematosus discussion subreddit
Lupus / Autoimmune Chat – Discord
https://discord.com/invite/JXdgGK6
https://discordapp.com/invite/7xxK8fa