BAFF Overexpression Is Associated with Autoantibody Production in Autoimmune Diseases

Abstract: The B‐cell activity factor (BAFF) acts as a positive regulator of B‐cell function. To gain further insight into the understanding of B‐cell hyperactivity in autoimmune diseases, the serum level of BAFF was determined in 43 systemic lupus erythematosus (SLE) patients, 58 primary Sjögren's syndrome (pSS) patients, 28 rheumatoid arthritis (RA) patients, and 68 normal control subjects using an in‐house sandwich ELISA. A commercial kit was used to detect soluble CD23 (sCD23) reflecting B‐cell activation. In‐house assays for the detection of autoantibodies also were used. We found an increased level of BAFF in SLE, pSS, and RA sera compared with normal subjects (respectively, 10.6 ± 8.5, 15.8 ± 12.9, 9.7 ± 1.5 ng/mL vs. 4.6 ± 2.9/ng/mL, P < .001). sCD23 released on B‐cell activation also was found to be elevated in SLE, pSS, and RA compared with normal sera. However, no correlation was found between the circulating BAFF and the level of sCD23. By contrast, we observed that high levels of BAFF were associated with the presence of autoantibodies (anti‐double‐stranded DNA antibodies in SLE, anti‐SSA antibodies in pSS, and rheumatoid factors in RA). Our data suggest that BAFF is influential in driving antibody production rather than activation of the B lymphocytes in autoimmune diseases.

[1]  J. Tschopp,et al.  BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth , 1999, The Journal of experimental medicine.

[2]  D. Vaux,et al.  Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[3]  V. Dixit,et al.  Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity , 2000, Nature Immunology.

[4]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[5]  E. Hay,et al.  Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome and systemic lupus erythematosus , 1992, Clinical and experimental immunology.

[6]  R. Jonsson,et al.  Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group , 2002, Annals of the rheumatic diseases.

[7]  S. Grey,et al.  The BAFF/APRIL system: an important player in systemic rheumatic diseases. , 2005, Current directions in autoimmunity.

[8]  F. Arnett.  Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[9]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[10]  G. Alarcón,et al.  Cutting Edge: A Role for B Lymphocyte Stimulator in Systemic Lupus Erythematosus1 , 2001, The Journal of Immunology.

[11]  X. Mariette,et al.  The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren’s syndrome , 2003, Annals of the rheumatic diseases.

[12]  V. Roschke,et al.  Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. , 2001, Arthritis and rheumatism.

[13]  W. Scherbaum,et al.  Organ-specific autoantibodies in non-organ-specific autoimmune diseases with special reference to rheumatoid arthritis , 2004, Rheumatology International.

[14]  Don Foster,et al.  TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease , 2000, Nature.

[15]  C. Mackay,et al.  B Cell-Activating Factor Belonging to the TNF Family (BAFF)-R Is the Principal BAFF Receptor Facilitating BAFF Costimulation of Circulating T and B Cells1 , 2004, The Journal of Immunology.

[16]  J. Tschopp,et al.  Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations , 1999, The Journal of experimental medicine.

[17]  J. Tschopp,et al.  Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome. , 2002, The Journal of clinical investigation.

[18]  Amy S Orr,et al.  BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. , 1999, Science.