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

Abstract

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.

Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity

“…BAFF elevation in the blood of SLE patients has been reported with consistency (41)(42)(43)(44)(45). IL-2 reports and its effects on immune function have varied.…”

“…Although BAFF may remain in an active membrane-bound form, soluble BAFF is required for B cell homeostasis and enhances the survival of plasmablasts (39,40). BAFF is elevated in the blood of SLE patients and is associated with the pathogenesis of SLE (41)(42)(43)(44)(45). BAFF-transgenic mouse studies demonstrated that overexpression of BAFF results in development of SLE-like autoimmune pathology including increased autoantibody production (46)(47)(48).…”

The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

“…BAFF-induced autoimmunity in BAFF Tg mice appears to be highly dependent on B cells and possibly the production of autoantibodies (11). High levels of BAFF have been found in the blood of patients with autoimmune diseases, particularly SLE and SS (10,(12)(13)(14)(15). And BAFF was also found on T lymphocytes infiltrating labial salivary glands from patients with SS (16).…”

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

“…Belimumab is a recombinant, human, immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that binds soluble B lymphocyte stimulator (BLyS) protein with high affinity and inhibits its biological activity2. BLyS is overexpressed in patients with SLE and correlates with severities in disease activity.…”