ORIGINAL ARTICLE Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys

eration Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison of monoclonal antibodies against human anti-BLyS and anti-APRIL in a common marmoset (Callithrix jacchus) model of experimental auto-immune encephalomyelitis (EAE). A MS-like disease was induced by immunization with recombinant human myelin/ oligodendrocyte glycoprotein (rhMOG) in complete Freund’s adjuvant. The results show that the anti-BLyS and anti-APRIL antibody cause significant depletion of circulating CD20+ B cells, but a small subset of CD20+CD40high B cells was not depleted. Induction of CD20+ B cell depletion from lymph nodes was only observed in the anti-BLyS treated monkeys. Both antibodies had a significant inhibitory ef-fect on disease development, but all monkeys developed clinically evident EAE. Anti-BLyS treated monkeys were sacrificed with the same clinical signs as saline-treated monkeys, but nevertheless displayed significantly reduced spinal cord demyelination. This effect was not observed in the anti-APRIL treated monkeys. The two antibodies had a different effect on T cell subset activation and the profiles of ex vivo released cytokines. In conclusion, treat-ment with anti-BLyS and anti-APRIL delays the develop-ment of neurological disease in a relevant preclinical model of MS. The two mAbs achieve this effect via different mechanisms