B lymphocyte stimulator expression in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis patients

Hong, Sandy; Reiff, Andreas; Yang, Haitao; Migone, Thi‐Sau; Ward, Christopher; Marzan, Katherine; Shaham, Bracha; Phei, Wee Choo; Garza, Judith; Bernstein, Bram; Stohl, William

doi:10.1002/art.24902

Cited by 24 publications

(15 citation statements)

References 44 publications

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“…BAFF mRNA may be a better marker than serum BAFF levels in the clinical monitoring of an SLE patient. Although contradictory to this, plasma BAFF levels but not BAFF mRNA levels correlated with disease activity in a study of paediatric SLE 58 …”

Section: Baff and Human Slementioning

confidence: 68%

BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus

2012

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Recently, the B cell has emerged as a cornerstone of systemic lupus erythematosus (SLE) pathogenesis. This has been highlighted by studies of the cytokine B-cell-activating factor of the tumour necrosis factor (TNF) family (BAFF), a crucial factor regulating B-cell maturation, survival and function. Overexpression of BAFF in mice leads to the development of an SLE-like disease, independent of T cells but instead relying on innate immunity mechanisms. Moreover, BAFF has been shown to be elevated in the serum of patients suffering from autoimmune conditions, especially SLE, and may correlate with disease activity. These findings challenge the previous notion that T:B-cell collaboration is the sole driver of SLE. In recent years, controlled trials have for the first time tested targeted therapeutics for SLE. However, agents designed to target B cells failed to meet primary endpoints in clinical trials in SLE, suggesting that a more complex role for B cells in SLE awaited elucidation. By contrast, on 9 March 2011, the US Food and Drug Administration approved belimumab, a fully human anti-BAFF monoclonal antibody, as a new B-cell-specific treatment for SLE. This article will review over 10 years of research on the BAFF system, key findings that led to this recent positive clinical outcome and propose a model potentially explaining why this B-cell-specific therapy has yielded positive results in clinical trials. We will also review promising therapies presently in clinical trials targeting innate immunity, which are likely to revolutionize SLE management towards a personalized and targeted therapy approach.

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Section: Baff and Human Slementioning

confidence: 68%

BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus

2012

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“…Elevated BAFF levels are associated with autoimmunity, most importantly Sjögren's syndrome and SLE (), and recently, therapeutic BAFF inhibition has been approved by the Food and Drug Administration for the treatment of SLE. Elevated BAFF levels have also been shown in active RA, whereas with respect to JIA, one study found higher BAFF levels (), and another group did not observe elevated BAFF levels in these patients (). In all of those studies, higher BAFF levels were associated with higher disease activity.…”

Section: Discussionmentioning

confidence: 99%

Distinct Effects of Methotrexate and Etanercept on the B Cell Compartment in Patients With Juvenile Idiopathic Arthritis

Glaesener

Quách

Onken

et al. 2014

Arthritis & Rheumatology

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ObjectiveB cells have been shown to play an important role in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Current treatments include the disease-modifying antirheumatic drugs methotrexate (MTX) and tumor necrosis factor α inhibition with etanercept. This study was undertaken to determine how these drugs influence the B cell compartment in patients with JIA.MethodsB cell subpopulations and follicular helper T (Tfh) cells in the peripheral blood of JIA patients were investigated by multicolor flow cytometry. Serum immunoglobulin and BAFF levels were determined by enzyme-linked immunosorbent assay.ResultsThere was a significant decrease in transitional B cells and significantly lower serum immunoglobulin levels in patients receiving MTX than in untreated patients and those receiving etanercept. In contrast, etanercept treatment had no effect on most of the B cell subpopulations, but resulted in significantly lower BAFF levels and increased numbers of Tfh cells. Thus, our findings indicate an unexpected and previously unknown direct effect of low-dose MTX on B cells, whereas etanercept had a more indirect influence.ConclusionOur results contribute to a better understanding of the potency of MTX in autoantibody-mediated autoimmune disease and present a possible mechanism of prevention of the development of drug-induced antibodies to biologic agents. The finding that MTX and etanercept affect the B cell compartment differently supports the notion that combination therapy with etanercept and MTX is more effective than monotherapy.

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“…Therefore, overproduction of BAFF might be associated with survival of autoreactive B cells. BAFF and APRIL overproduction has been shown in multiple autoimmune diseases (234)(235)(236)(237)(238)(239). Moreover, the stimulation of one of the BAFF-Rs, namely BCMA, has been shown in vitro to increase the survival of human memory B cells and of plasmablast generated from memory B cells (240).…”

Section: Autoreactive Memory B and Memory Pcsmentioning

confidence: 99%

Memory B and memory plasma cells

Yoshida

Mei

Dörner

et al. 2010

Immunological Reviews

247

222

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Vaccination provides a powerful means to control infections. It exploits and exemplifies the ability of the immune system to preserve the information that a specific pathogen has been encountered in the past. The cells and molecular mechanisms of immunological memory are still being discussed controversially. Here, we review the current concepts of memory B cells, the signals involved in their maintenance, and their role in enhanced secondary reactions. Memory plasma cells, secreting protective antibodies over lifetime, have been recognized only recently. Their characterization as cells resting in terms of proliferation and migration, and surviving in dedicated stromal niches, in the absence of antigen, has generated new concepts of how memory cells in general are organized by stroma cells, the 'resting memory'. In autoimmunity and chronic inflammation, memory B cells and memory plasma cells can be essential players, and they require special attention, as they do not respond to most conventional therapies. Their selective targeting will depend on a molecular understanding of their lifestyle.

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B lymphocyte stimulator expression in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis patients

Cited by 24 publications

References 44 publications

BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus

BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus

Distinct Effects of Methotrexate and Etanercept on the B Cell Compartment in Patients With Juvenile Idiopathic Arthritis

Memory B and memory plasma cells

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