Collectively, our results have identified and confirmed APRIL as a new target involved in B-cell activation, in the maintenance of plasma cell survival and subsequent increased autoantibody production that sustains lupus development in mice.
These include the BAFF/APRIL dual inhibitor, atacicept, and the BAFF inhibitor, belimumab, which is approved as an add-on therapy for patients with active SLE.
Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus.
We previously reported the association of APRIL haplotypes formed by two nonsynonymous polymorphisms, Gly67Arg and Asn96Ser, with systemic lupus erythematosus.
The APRIL codon 67 was significantly associated with SLE risk under the dominant model adjusted by ethnicity (odds ratio, 95% confidence interval and P-values were 1.45 and 1.02-2.06 and 0.036, respectively).
The protective effect of APRIL c.199A/A homozygotes in SLE was replicated (odds ratio 0.50, 95% confidence interval 0.30-0.83, P = 0.0073; pooled P = 0.0001, Pcorr = 0.007).