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J Neuroimmune Pharmacol. 2012 Sep;7(3):557-70. doi: 10.1007/s11481-012-9384-x. Epub 2012 Jun 30.

Antibodies against human BLyS and APRIL attenuate EAE development in marmoset monkeys.

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1
Department Immunobiology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH, Rijswijk, The Netherlands.

Erratum in

  • J Neuroimmune Pharmacol. 2013 Mar;8(1):370. Oh, Luke [added].

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.

PMID:
22870852
PMCID:
PMC3419352
DOI:
10.1007/s11481-012-9384-x
[Indexed for MEDLINE]
Free PMC Article
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