B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid                 arthritis in relation to autoantibody levels, disease measures and time

Becker-Merok, Andrea; Nikolaisen, Cathrin; Nossent, Jiri

doi:10.1177/0961203306071871

Cited by 116 publications

(93 citation statements)

References 34 publications

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“…3A). The BAFF levels in APS I patients were comparable to those found in patients who have other autoimmune diseases in which autoantibodies are involved in the pathology (e.g., anti-doublestranded DNA antibodies in systemic lupus erythematosus, anti-SSA antibodies in primary Sjögren's syndrome, and rheumatoid factors in rheumatoid arthritis) (18,(24)(25)(26). In contrast, serum levels of a proliferation-inducing ligand (APRIL), another member of the TNF family that shares the transmembrane activation and calcium-modulator and cytophilin ligand interaction (TACI) and B-cell maturation antigen (BCMA) receptors with BAFF, were not elevated in APS I patients (Fig.…”

Section: Aire Deficiency Leads To Increased Levels Of Baff Through a supporting

confidence: 57%

AIRE regulates T-cell-independent B-cell responses through BAFF

Lindh

Lind

Lindmark

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Autoimmune polyendocrine syndrome type I (APS I) results in multiple endocrine organ destruction and is caused by mutations in the autoimmune regulator gene (AIRE). APS I is characterized by circulating tissue-specific autoantibodies, and the presence of these antibodies is often predictive of organ destruction. The importance of AIRE in ensuring central tolerance by regulating the negative selection of autoreactive T cells has been shown clearly. However, in Aire ؊/؊ mice the phenotype (i.e., autoantibodies, liver infiltrates of B cells, splenomegaly, and marginal zone B-cell lymphoma) is predominantly B-cell mediated, suggesting an exaggerated activation of B cells. We have studied T-cell-independent B-cell responses in the absence of AIRE and found that Aire ؊/؊ mice have an increased response against T-cell-independent type II antigens. We linked this exaggerated response to the elevated serum levels of the B-cell-activating factor of the TNF family (BAFF) that were found both in APS I patients and in Aire ؊/؊ mice. Transfer of Aire ؊/؊ bone marrow into irradiated nude mice resulted in increased percentage of BAFF-expressing antigenpresenting cells compared with wt bone marrow, suggesting a T-cell-independent mechanism behind our findings. Furthermore, in vitro experiments showed that AIRE-deficient murine bone marrowderived dendritic cells produced significantly more BAFF than wt cells when stimulated with IFN-␥ but not when stimulated with IL-10. Our results suggest a cell-intrinsic role for AIRE in peripheral dendritic cells by regulating IFN-␥-receptor signaling and point toward complementary mechanisms by which AIRE is involved in maintaining tolerance.autoimmunity ͉ tolerance

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Section: Aire Deficiency Leads To Increased Levels Of Baff Through a supporting

confidence: 57%

AIRE regulates T-cell-independent B-cell responses through BAFF

Lindh

Lind

Lindmark

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…These results suggest that there is no direct relationship between levels of BLyS and IL-6 as markers of B-cell proliferation and B-cell autoantibody secretion in RA patients. Except for Sjögren's syndrome [54], a significant correlation between BLyS and autoantibodies is rarely in found in RA as in other systemic autoimmune diseases [55], as we have observed in mixed cryoglobulinaemic syndrome [56] and in an extended RA series (unpublished personal observations). Local, rather than systemic levels of both autoantibodies and pivotal disease cytokines could be more representative of disease activity in RA [57].…”

Section: Discussionsupporting

confidence: 53%

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

Fabris¹,

Vita

Blasone³

et al. 2010

Autoimmun Highlights

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at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine, chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month +6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation, interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a-CCP, nor RF IgA compared to routine total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.

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“…by guest www.bloodjournal.org From factors in RA). However, some studies found that BAFF levels did not correlate with autoantibody titers in SLE 35 ; BAFF stimulation of B cells may contribute to SLE by mechanisms other than autoantibody production. In our study, no association was found between the levels of BAFF and antiplatelet autoantibodies, and addition of rhBAFF did not promote the production of autoantibodies in vitro.…”

Section: Discussionmentioning

confidence: 96%

The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

Zhu

Shi

Peng

et al. 2009

Blood

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IntroductionImmune thrombocytopenia (ITP) is an autoimmune disorder in which the patient's immune system is activated by platelet autoantigens resulting in immune-mediated platelet destruction and/or suppression of platelet production. 1 The autoantibodies produced by autoreactive B cells against self-antigens, specifically immunoglobulin G (IgG) antibodies against glycoprotein IIb (GPIIb)/IIIa and/or GPIb/IX, are considered to play a crucial role. 2 In addition, several abnormalities involving the cellular mechanisms of immune modulation, such as the T helper 1 (Th1) bias, 3,4 the decreased number or defective suppressive function of regulatory T cells, 5-7 and the platelet destruction by cytotoxic T cells (CTLs), [8][9][10] have been described. The cause for these abnormalities remains unknown. Moreover, the treatment regimens for ITP including glucorticosteroids, intravenous immunoglobulin G, anti-D, and splenectomy are not always effective, and only one-third of adult patients achieve long-term remission.B-cell activating factor (BAFF; also known as B-lymphocyte stimulator, tumor necrosis factor and apoptosis ligand-related leukocyte-expressed ligand 1, tumor necrosis factor homologue that activates apoptosis, nuclear factor B, and c-Jun NH 2 -terminal kinase, and tumor necrosis factor superfamily 13B) belonging to the family of tumor necrosis factor (TNF) ligands is critical for the maintenance of normal B-cell development, homeostasis, and autoreactivity 11,12 and T-cell costimulation. [13][14][15] In addition, BAFF also augments certain Th1-associated inflammatory responses. 16 BAFF binds to 3 receptors: B-cell maturation antigen (tumor necrosis factor receptor superfamily, member 17 [TNFRSF17]), transmembrane activator and calcium-modulating cyclophilin ligand (CAML) interactor (TACI; TNFRSF13B), and BAFF receptor (BR3/BAFF-R; TNFRSF13C). 17,18 BR3, identified as the crucial receptor for B-cell survival, is expressed on a wide range of B-cell subsets, including immature, transitional, mature, memory, and germinal center B cells, as well as on plasma cells. 19 Furthermore, BAFF binding to BR3 on T cells has been shown to costimulate T-cell proliferation both in vitro and in vivo. 15 Several lines of evidence suggested that BAFF may play an important role in autoimmunity. Autoantigen-binding B cells may have an increased dependence on the BAFF survival signal. 20 In addition, elevated BAFF plasma level was observed in many patients with autoimmune diseases such as rheumatoid arthritis (RA), 21 systemic lupus erythematosus (SLE), 22 Sjögren syndrome (SS), 23 and multiple sclerosis. 24 Inhibition of BAFF signaling is a potentially therapeutic option for treatment of B cell-mediated autoimmune conditions. Data from animal tests and clinical trials had proved that blockade of BAFF by blocking reagents (TACI-Ig, BAFF-R-Ig, BR3-Fc) was an effective therapeutic approach for some autoimmune diseases. [25][26][27] In our study, we focused on the effects of BAFF and BR3-Fc in ITP, and found recombinant human BAFF (r...

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B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in relation to autoantibody levels, disease measures and time

Cited by 116 publications

References 34 publications

AIRE regulates T-cell-independent B-cell responses through BAFF

AIRE regulates T-cell-independent B-cell responses through BAFF

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

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