BAFF and APRIL roles in SLE pathogenesis are reviewed

The review examines BAFF's role in systemic lupus erythematosus and notes that belimumab, a BAFF-neutralizing antibody, showed efficacy in a randomized clinical trial in 2011; it also reports that APRIL's role in SLE is less well understood.

Systemic lupus erythematosus (SLE) is presented as a multisystem immune-mediated condition driven by autoimmunity to nuclear antigens. The review discusses how clinical heterogeneity, the lack of universally agreed trial end points, and few validated therapeutic targets have limited novel SLE treatments. It highlights that belimumab, a monoclonal antibody that neutralizes BAFF, became the first targeted therapy to show efficacy in a randomized clinical trial in 2011. The authors focus on BAFF because the related cytokine APRIL is less well characterized in SLE. Key points: - Belimumab neutralizes BAFF and demonstrated efficacy in a randomized clinical trial in 2011. - Belimumab causes B-cell depletion, but this effect is less marked than that seen with some other B-cell–directed therapies that have not shown efficacy in randomized trials. - The review suggests that neutralizing BAFF can have immune effects beyond simple B-cell depletion. - Differences in the molecular forms of BAFF might affect the efficacy of BAFF-specific therapies. - APRIL's role in SLE is reported as much less well understood, so the review concentrates mainly on BAFF. Summary: The authors emphasize BAFF as a biologically relevant factor in SLE and note that therapy responses could depend on molecular differences in BAFF. They identify gaps in current data and propose studies aimed at clarifying BAFF's roles and refining anti-BAFF approaches. Undetermined at this time.