Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys
B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation 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 autoimmune 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 + CD40highB 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 effect 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, treatment with anti-BLyS and anti-APRIL delays the development of neurological disease in a relevant preclinical model of MS. The two mAbs achieve this effect via different mechanisms.
|Keywords||B-cell Depletion, Cytokines, EAE, Multiple sclerosis, Non-human primate|
|Persistent URL||dx.doi.org/10.1007/s11481-012-9384-x, hdl.handle.net/1765/32877|
Jagessar, S.A., Heijmans, N., Bauer, J., Blezer, E., Laman, J.D., Migone, T.S., … 't Hart, B.. (2012). Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys. Journal of Neuroimmune Pharmacology, 1–14. doi:10.1007/s11481-012-9384-x