Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus

Objective To determine the association of plasma B lymphocyte stimulator (BLyS) levels, immunosuppressive therapy, and other clinical parameters with disease activity in systemic lupus erythematosus (SLE). Methods Two hundred forty‐five SLE patients were evaluated prospectively over a 2‐year period at 4 centers. Assessments were performed every 3–6 months. Univariate analysis was used to determine the association among the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, serum anti–double‐stranded DNA (anti‐dsDNA), and plasma BLyS levels. A multivariate repeated‐measures model incorporating immunosuppressive therapy was utilized. Results Ninety‐two percent of the patients were female. Sixty‐seven percent were white, 31% African American, and 2% Asian (all of these groups may include Hispanic). Mean values at baseline were as follows: age 41.5 years, disease duration 8.1 years, SELENA–SLEDAI 3.3 (median 2, range 0–18), BLyS 5.57 ng/ml, IgG 1,439 mg/dl, C3 104.4 mg/dl, and C4 21.3 mg/dl; among those positive for anti‐dsDNA, the median titer was 1:40 (range 1:10–1:1,280). Univariate analysis showed that plasma BLyS levels were associated with anti‐dsDNA titers ( P = 0.0465) and SELENA–SLEDAI scores ( P = 0.0002). In multivariate analyses, a greater increase in the SELENA–SLEDAI score from the previous visit was associated with higher BLyS levels at the previous visit ( P = 0.0042) and with a greater increase in the BLyS level from the previous visit ( P = 0.0007). Conclusion The findings of association between a greater increase in the BLyS level from the previous visit and a greater increase in the SELENA–SLEDAI score at the subsequent visit, and between an elevated BLyS level at the previous visit and a greater SELENA–SLEDAI score at the subsequent visit, demonstrate a relationship between circulating BLyS levels and SLE disease activity. These results lend support to the notion that BLyS is a candidate for therapeutic targeting in SLE.