Background: Recent experimental observations support a dominant role of B lymphocytes in the pathogenesis of Rheumatoid Arthritis (RA)(1). Objectives: To define the role of B-Lymphocytes Stimulator in RA. BLyS appears one of the most important players in this scenario, since it is produced by monocytes and dendritic cells and acts on mature B-cells promoting survival, proliferation and Ig secretion. Methods: The study included 77 consecutive RA patients fulfilling the American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for RA. The mean age was 57.2 ± 13.1 years and the mean disease duration was 11.8 ± 12.3 years. 40 age and sex-matched blood donors were taken as controls. All the patients were evaluated by clinical examination and laboratory tests and the Disease Activity Score (DAS28) was calculated. Seven patients were evaluated at baseline and after 3 and 6 months of anti-TNFalpha therapy. Plasma levels of BLyS, IgA and IgM-Rheumatoid Factor (RF) and anti-CCP antibodies were assessed by ELISA, following the manufacturer''s instructions. Results: BLyS plasma levels were significantly higher in RA patients than in controls (4.48±2.96 ng/ml versus 3.37±0.78, p=0.048 Mann Whitney non parametric T-test) and 26% of the patients presented a titer above range of normality, defined by the 95° percentile of the control distribution (4.97 ng/ml). All the patients with high BLyS levels had a long disease duration (>1year) and were widely resistant to DMARDs therapy. We found a significant positive correlation between BlyS and the parameters of disease activity: swollen joint count and DAS score (r= 0.4, p=0.0001; r=0.3, p=0.0023, respectively). No correlation was found with acute phase reactants (ESR, CRP) or with the levels of the autoantibodies (IgM RF and IgA RF anti-CCp). Finally, anti-TNFa therapy led to a simultaneous decrease of DAS, SJC and BlyS. Conclusion: BLyS seems to reflect the severity of the synovial burden in RA inflammation of long disease duration. The lack of correlation between BLyS and IgM and IgA RF or anti-CCP antibody levels, seems to suggest that this cytokine, while characterizing the mature stages of the disease, does not influence the loss of tolerance occurring in RA development. References: 1. Tan SM et al., Arthritis Rheum 2003; 48: 982-92
B-lymphocyte stimulator (BLYS) in rheumatoid arthritis: clinical, biological and prognostic relevance
Gremese E;
2005-01-01
Abstract
Background: Recent experimental observations support a dominant role of B lymphocytes in the pathogenesis of Rheumatoid Arthritis (RA)(1). Objectives: To define the role of B-Lymphocytes Stimulator in RA. BLyS appears one of the most important players in this scenario, since it is produced by monocytes and dendritic cells and acts on mature B-cells promoting survival, proliferation and Ig secretion. Methods: The study included 77 consecutive RA patients fulfilling the American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for RA. The mean age was 57.2 ± 13.1 years and the mean disease duration was 11.8 ± 12.3 years. 40 age and sex-matched blood donors were taken as controls. All the patients were evaluated by clinical examination and laboratory tests and the Disease Activity Score (DAS28) was calculated. Seven patients were evaluated at baseline and after 3 and 6 months of anti-TNFalpha therapy. Plasma levels of BLyS, IgA and IgM-Rheumatoid Factor (RF) and anti-CCP antibodies were assessed by ELISA, following the manufacturer''s instructions. Results: BLyS plasma levels were significantly higher in RA patients than in controls (4.48±2.96 ng/ml versus 3.37±0.78, p=0.048 Mann Whitney non parametric T-test) and 26% of the patients presented a titer above range of normality, defined by the 95° percentile of the control distribution (4.97 ng/ml). All the patients with high BLyS levels had a long disease duration (>1year) and were widely resistant to DMARDs therapy. We found a significant positive correlation between BlyS and the parameters of disease activity: swollen joint count and DAS score (r= 0.4, p=0.0001; r=0.3, p=0.0023, respectively). No correlation was found with acute phase reactants (ESR, CRP) or with the levels of the autoantibodies (IgM RF and IgA RF anti-CCp). Finally, anti-TNFa therapy led to a simultaneous decrease of DAS, SJC and BlyS. Conclusion: BLyS seems to reflect the severity of the synovial burden in RA inflammation of long disease duration. The lack of correlation between BLyS and IgM and IgA RF or anti-CCP antibody levels, seems to suggest that this cytokine, while characterizing the mature stages of the disease, does not influence the loss of tolerance occurring in RA development. References: 1. Tan SM et al., Arthritis Rheum 2003; 48: 982-92I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
