title: Antibodies against human BLyS and APRIL attenuate EAE development in marmoset monkeys.
abstract: 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 + CD40(high) 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 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.
authors.affiliation: Department Immunobiology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH, Rijswijk, The Netherlands.
authors.forename: S Anwar
authors.initials: SA
authors.lastname: Jagessar
authors.forename: Nicole
authors.initials: N
authors.lastname: Heijmans
authors.forename: Luke
authors.initials: L
authors.lastname: Oh
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Erwin L A
authors.initials: EL
authors.lastname: Blezer
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: Matt N
authors.initials: MN
authors.lastname: Devalaraja
authors.forename: Bert A
authors.initials: BA
authors.lastname: 't Hart
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D002144:Callithrix; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D011897:Random Allocation; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13