The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren's syndrome

Abstract

Background: Increased levels of B lymphocyte stimulator (BLyS) have been detected in serum from patients with systemic lupus erythematosus and rheumatoid arthritis.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Figure 1

BLyS levels in patients with SS. (A) Serum levels of BLyS in the patients with SS (n=49) were significantly higher than in normal donors (n=47), p<0.001. (B and C) Among patients with SS, BLyS levels were higher in patients with anti-SSA antibodies, anti-SSB antibodies, and in patients with RF (p=0.008, p=0.02, and p=0.016, respectively; Mann-Whitney test). The medians of each group were: normal, 2.49 ng/ml; SS, 5.99 ng/ml; SS with anti-SSA, 7.90 ng/ml; SS with anti-SSB, 7.14 ng/ml; SS without anti-SSA/SSB, 3.70 ng/ml; SS with RF, 7.70 ng/ml; SS without RF, 3.80 ng/ml.

Figure 2

Correlation between BLyS and immunoglobulins. Correlations between serum levels of BLyS and serum gammaglobulin (A), and IgG (B) were determined for the 46 patients with SS without a monoclonal component. Analysis was based on log₁₀ transformed values. The correlation coefficient was determined by the Pearson product statistic and the regression line is represented by the solid line.

Figure 3

Correlation between BLyS and autoantibodies. Correlations between serum levels of BLyS and anti-SSA IgG (A), anti-SSA IgM (B) and serum RF (C) were determined by log₁₀ transformed values. The correlation coefficient was determined by the Pearson product statistic and the regression line is represented by the solid line.