Abstract
Increased levels of B lymphocyte stimulator (BLyS) have been detected in serum from patients with systemic lupus erythematosus and rheumatoid arthritis. To determine the level of BLyS in serum from patients with primary's Sjögren's syndrome (SS), another autoimmune disease in which B cell activation is high. Serum samples from 49 patients with primary SS according to the revised European criteria were assayed for BLyS, quantitative immunoglobulins, and autoantibody levels and compared with samples from 47 healthy control subjects. The median level of BLyS was 5.99 ng/ml (25th-75th centile range 3.20-8.93 ng/ml) in SS v 2.49 ng/ml (25th-75th centile range 1.96-2.96 ng/ml) in healthy controls (p<0.001). More importantly, among patients with SS, the presence of anti-SSA antibodies was associated with significantly higher levels of BLyS (medians 7.90 ng/ml v 3.70 ng/ml; p=0.008) as was the presence of anti-SSB antibodies (medians 7.14 ng/ml v 3.70 ng/ml; p=0.02) and of rheumatoid factor (medians 7.70 ng/ml v 3.80 ng/ml; p=0.016). The level of BLyS in three patients with a monoclonal gammopathy was higher than in the other patients (medians 26.53 ng/ml v 5.92 ng/ml; p=0.13). Higher levels of BLyS were associated with higher levels of gammaglobulins and IgG. There was a strong correlation between BLyS and rheumatoid factor level (r=0.71, p<0.0001), anti-SSA IgG level (r=0.32, p=0.02) and anti-SSA IgM level (r=0.39, p=0.006). In human SS the level of BLyS correlates with the level of autoantibodies. Thus, BLyS may play a part in activating specific autoreactive B cells and modulating the level of production of autoantibodies which are the hallmark of the disease. These findings raise the possibility of a novel therapeutic approach in human SS.
MeSH Terms
Antibodies, Antinuclear/blood
Autoantibodies/blood
Autoimmune Diseases/immunology
B-Cell Activating Factor
Enzyme-Linked Immunosorbent Assay/methods
Humans
Immunoglobulins/blood
Membrane Proteins/blood
Rheumatoid Factor/blood
Sjogren's Syndrome/immunology
Tumor Necrosis Factor-alpha
Chemicals
Antibodies, Antinuclear
Autoantibodies
B-Cell Activating Factor
Immunoglobulins
Membrane Proteins
SS-A antibodies
SS-B antibodies
TNFSF13B protein, human
Tumor Necrosis Factor-alpha
Rheumatoid Factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Mariette X
Service de Rhumatologie, Hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, Université Paris XI, INSERM EMI 0109, 94275 Le Kremlin Bicêtre, France. xavier.mariette@bct.ap-hop-paris.fr
Roux S
Zhang J
Bengoufa D
Lavie F
Zhou T
Kimberly R
References (18)
18 references, click to expand
-
Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
Science. 1999 Nov 26;286(5445):1732-5
PMID: 10576739
-
BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator.
Science. 1999 Jul 9;285(5425):260-3
PMID: 10398604
-
Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice.
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3370-5
PMID: 10716715
-
TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease.
Nature. 2000 Apr 27;404(6781):995-9
PMID: 10801128
-
Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus.
J Immunol. 2001 Jan 1;166(1):6-10
PMID: 11123269
-
Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases.
Arthritis Rheum. 2001 Jun;44(6):1313-9
PMID: 11407690
-
TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice.
Nat Immunol. 2001 Jul;2(7):632-7
PMID: 11429548
-
Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease.
Nat Immunol. 2001 Aug;2(8):746-53
PMID: 11477412
-
BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF.
Science. 2001 Sep 14;293(5537):2108-11
PMID: 11509692
-
Lymphomas complicating Sjögren's syndrome and hepatitis C virus infection may share a common pathogenesis: chronic stimulation of rheumatoid factor B cells.
Ann Rheum Dis. 2001 Nov;60(11):1007-10
PMID: 11602464
-
Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome.
J Clin Invest. 2002 Jan;109(1):59-68
PMID: 11781351
-
Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.
Ann Rheum Dis. 2002 Jun;61(6):554-8
PMID: 12006334
-
A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma.
EMBO J. 1992 Nov;11(11):3897-904
PMID: 1396583
-
Salazosulfapyridine suppresses chondrocyte mediated degradation induced by interleukin 1beta.
J Rheumatol. 1997 Mar;24(3):550-4
PMID: 9058664
-
From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins.
Immunity. 1999 Apr;10(4):451-61
PMID: 10229188
-
TALL-1 is a novel member of the TNF family that is down-regulated by mitogens.
J Leukoc Biol. 1999 May;65(5):680-3
PMID: 10331498
-
BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.
J Exp Med. 1999 Jun 7;189(11):1747-56
PMID: 10359578
-
Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.
J Exp Med. 1999 Dec 6;190(11):1697-710
PMID: 10587360