PT - JOURNAL ARTICLE AU - Leticia Fernandez AU - Gabriela Franco Salinas AU - Cecilia Rocha AU - Carla E Carvalho-Pinto AU - Nataliya Yeremenko AU - Laura Papon AU - Jan Paul Medema AU - Bernard Combe AU - Jacques Morel AU - Dominique Baeten AU - Michael Hahne TI - The TNF family member APRIL dampens collagen-induced arthritis AID - 10.1136/annrheumdis-2012-202382 DP - 2013 Aug 01 TA - Annals of the Rheumatic Diseases PG - 1367--1374 VI - 72 IP - 8 4099 - http://ard.bmj.com/content/72/8/1367.short 4100 - http://ard.bmj.com/content/72/8/1367.full SO - Ann Rheum Dis2013 Aug 01; 72 AB - Background The tumour necrosis factor (TNF)-family members B cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) play important roles in B cell biology, and share binding to B cell maturation antigen and transmembrane activator and cyclophilin ligand interactor, both receptors of the TNF-family. However, while it is reported that BAFF can break B cell tolerance, the role of APRIL in autoimmunity remains elusive. Objective To evaluate the role of APRIL on collagen-induced arthritis (CIA). Methods CIA was induced in APRIL-transgenic (Tg) DBA/1 mice and littermates. Disease progression was evaluated by clinical and histological signs of arthritis. In another experimental setting mice were exposed to the collagen antibody-induced arthritis. In addition, we tested T cell dependent humoral responses in APRIL-Tg mice. Results We found that APRIL-Tg displayed a strongly reduced incidence and severity of CIA compared with littermates, with decreases in collagen-specific autoantibody titres, immune complex deposition and downstream mast cell activation in joints. Notably, ectopic APRIL-expression was also found to negatively regulate T cell dependent humoral responses. The lower autoantibody production in APRIL-Tg mice during CIA appears to be crucial, as arthritis induced by administration of anti-collagen antibodies developed similar in APRIL-Tg and control mice, thus demonstrating that the downstream effector pathways induced by anti-collagen antibodies remain intact in APRIL-Tg mice. This protective effect was specifically mediated by APRIL, as adenoviral delivery of APRIL decreased CIA in a therapeutic setting. Conclusions Collectively, our data identify APRIL as a negative regulator of CIA by regulating autoantibody production. These findings are of important clinical relevance, as the therapeutic potential of transmembrane activator and cyclophilin ligand interactor-Fc (atacicept) is presently evaluated in clinical trials.