| Autor: |
Jagessar SA; Department Immunobiology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH, Rijswijk, The Netherlands., Heijmans N, Oh L, Bauer J, Blezer EL, Laman JD, Migone TS, Devalaraja MN, 't Hart BA |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2012 Sep; Vol. 7 (3), pp. 557-70. Date of Electronic Publication: 2012 Jun 30. |
| DOI: |
10.1007/s11481-012-9384-x |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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