Circulating B-cell activating factor levels' dependence on treatment in patients with systemic lupus erythematosus

Success of B cell-targeted treatments in autoimmune diseases has brought into focus B cell hyperactivity as a dominant disorder. B-cell activating factor (BAFF) is a homeostatic cytokine essential for development, maturation and survival of peripheral B cell pool. As it seems that BAFF can promote B cell survival in the absence of BCR activation, its upregulation could aid the breach of tolerance in B cell-dependent autoimmune diseases such as systemic lupus erythematosus (SLE). Indeed, several reports link increased BAFF mRNA and protein levels in a subgroup of SLE patients with disease activity and autoantibody levels. Moreover, BAFF transgenic mice develop anti-double-stranded DNA antibodies, nephritis and salivary gland destruction even in absence of T-cell help. We measured serum BAFF protein levels by ELISA in eleven newly-discovered SLE patients in four time-points: before treatment (Tx), after three weeks of glucocorticoid Tx, after three months when steroids were tapered and chloroquine introduced, and after two years, where Tx was modified according to individual’ s status. We found that patients on glucocorticoids only have significantly lower BAFF levels than healthy controls, but the difference is lost when steroid dose was lowered. Between-group analysis showed that patients on steroids ± chloroquine had lower BAFF levels than untreated patients and at two-year follow-ups. In vitro experiments on isolated healthy human peripheral blood leukocytes demonstrated that glucocorticoids up-regulate BAFF-receptor expression on B cells, whereas chloroquine has no effect. Thus, glucocorticoid treatment and dose should be taken into account when interpreting BAFF levels in patients with SLE.