Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore

Abstract

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

Smoking associates with increased BAFF and decreased interferon-γ levels in patients with systemic lupus erythematosus

“… 5 44 The overexpression of BAFF in SLE is hypothesised to be driven by localised inflammation or B cell activation resulting from inherent immune dysregulation in SLE. 30 45 BAFF levels have also been associated with disease activity 46 and organ damage 47 48 in some but not all cohort studies. 45 Yet, the failure of monoclonal anti-BAFF therapy to dampen disease activity 49 suggests that aberrant BAFF production is a feature rather than a direct cause of lupus disease activity.…”

Anti-Cytokine Autoantibodies in Systemic Lupus Erythematosus

“…In contrast, a Swiss study of adult SLE patients did not demonstrate an increase in anti-BAFF autoantibody levels or any association with SLE disease activity while serum BAFF-IgG complexes were associated with serological and clinical SLE disease activity [13]. We recently observed elevated levels of anti-BAFF antibodies in the majority of our multi-ethnic Asian SLE patients, which correlated negatively with clinical disease activity, levels of anti-dsDNA antibodies, and serum BAFF, suggesting that they may be immunomodulatory in nature and may serve as a tool in monitoring disease progression [54].…”

“…Several recent studies have reported raised levels of endogenous anti-BAFF autoantibodies in SLE both in adult [53,54] as well as in pediatric patients [55]. Raised anti-BAFF autoantibody levels were found to correlate with disease activity in pediatric SLE patients [55].…”

Review article: targeting the B cell activation system in autoimmune hepatitis

“…Furthermore, the circulating BAFF levels have correlated with disease‐associated antibody levels in SLE, 62,238 rheumatoid arthritis, 74 and Sjogren's syndrome 77 . A negative correlation between the serum level of antibodies to BAFF (anti‐BAFF) and disease activity in SLE has supported the concept of BAFF as a pathogenic factor 240 …”

“…BAFF has been implicated as a biomarker for disease activity and a pathogenic factor in patients with SLE, 62,70,238‐242 rheumatoid arthritis, 72,74 and Sjogren's syndrome (Table 4). 76,77 The over‐expression of BAFF has been demonstrated by increased serum levels of soluble BAFF in patients with SLE, 62,239‐241 rheumatoid arthritis, 72,74 and Sjogren's syndrome 76,77 and by increased levels of mRNA for BAFF in the leukocytes of patients with active SLE 65,66,238,239 . Furthermore, the circulating BAFF levels have correlated with disease‐associated antibody levels in SLE, 62,238 rheumatoid arthritis, 74 and Sjogren's syndrome 77 .…”