scholarly journals Signaling Lymphocytic Activation Molecule Family Member 1 Engagement Inhibits T Cell–B Cell Interaction and Diminishes Interleukin‐6 Production and Plasmablast Differentiation in Systemic Lupus Erythematosus

2018 ◽  
Vol 71 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Maria P. Karampetsou ◽  
Denis Comte ◽  
Abel Suárez‐Fueyo ◽  
Eri Katsuyama ◽  
Nobuya Yoshida ◽  
...  
2017 ◽  
Vol 69 (5) ◽  
pp. 1035-1044 ◽  
Author(s):  
Denis Comte ◽  
Maria P. Karampetsou ◽  
Nobuya Yoshida ◽  
Katalin Kis‐Toth ◽  
Vasileios C. Kyttaris ◽  
...  

2019 ◽  
Vol 20 (24) ◽  
pp. 6231 ◽  
Author(s):  
Desmond Y. H. Yap ◽  
Tak Mao Chan

Abnormalities in B cells play pivotal roles in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). Breach in central and peripheral tolerance mechanisms generates autoreactive B cells which contribute to the pathogenesis of SLE and LN. Dysregulation of B cell transcription factors, cytokines and B cell–T cell interaction can result in aberrant B cell maturation and autoantibody production. These immunological abnormalities also lead to perturbations in circulating and infiltrating B cells in SLE and LN patients. Conventional and novel immunosuppressive medications confer differential effects on B cells which have important clinical implications. While cyclophosphamide and mycophenolate mofetil (MMF) showed comparable clinical efficacy in active LN, MMF induction was associated with earlier reduction in circulating plasmablasts and plasma cells. Accumulating evidence suggests that MMF maintenance is associated with lower risk of disease relapse than azathioprine, which may be explained by its more potent and selective suppression of B cell proliferation. Novel therapeutic approaches targeting the B cell repertoire include B cell depletion with monoclonal antibodies binding to cell surface markers, inhibition of B cell cytokines, and modulation of costimulatory signals in B cell–T cell interaction. These biologics, despite showing improvements in serological parameters and proteinuria, did not achieve primary endpoints when used as add-on therapy to standard treatments in active LN patients. Other emerging treatments such as calcineurin inhibitors, mammalian target of rapamycin inhibitors and proteasome inhibitors also show distinct inhibitory effects on the B cell repertoire. Advancement in the knowledge on B cell biology has fueled the development of new therapeutic strategies in SLE and LN. Modification in background treatments, study endpoints and selective recruitment of subjects showing aberrant B cells or its signaling pathways when designing future clinical trials may better elucidate the roles of these novel therapies for SLE and LN patients.


2012 ◽  
Vol 64 (9) ◽  
pp. 2953-2963 ◽  
Author(s):  
Shu Ding ◽  
Yunsheng Liang ◽  
Ming Zhao ◽  
Gongping Liang ◽  
Hai Long ◽  
...  

2000 ◽  
Vol 106 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Masahiko Mihara ◽  
Irene Tan ◽  
Yelena Chuzhin ◽  
Bhoompally Reddy ◽  
Lalbachan Budhai ◽  
...  

2021 ◽  
Author(s):  
Quentin Moyon ◽  
Delphine Sterlin ◽  
Makoto Miyara ◽  
Francois Anna ◽  
Alexis Mathian ◽  
...  

Objectives: Our aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination. Methods: In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-gamma; release assay after the second dose. Results: BNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (beta=-78; p=0.007, beta=-122; p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total IgG serum levels, naive B cell frequencies (beta=2; p=0.018, beta=2.5; p=0.003) and SARS-CoV-2-specific T cell response (r=0.462; p=0.003). In responders, serum neutralization activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients. Conclusion: MMF, MTX and poor baseline humoral immune status, particularly: low naive B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up.


Immunology ◽  
2007 ◽  
Vol 122 (3) ◽  
pp. 371-380 ◽  
Author(s):  
Sophie Hillion ◽  
Soizic Garaud ◽  
Valérie Devauchelle ◽  
Anne Bordron ◽  
Christian Berthou ◽  
...  

2013 ◽  
Vol 74 (2) ◽  
pp. 452-463 ◽  
Author(s):  
Khader Valli Rupanagudi ◽  
Onkar P Kulkarni ◽  
Julia Lichtnekert ◽  
Murthy Narayana Darisipudi ◽  
Shrikant R Mulay ◽  
...  

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