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Prevention of experimental autoimmune encephalomyelitis in the common marmoset (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against human CD40 is associated with altered B cell responses
- Source :
- Journal of Immunology, 167, 2942-2949. American Association of Immunologists, Jan Bauer, Scopus-Elsevier
- Publication Year :
- 2001
-
Abstract
- Inhibition of CD40-CD40 ligand interaction is a potentially effective approach for treatment of autoimmune diseases, such as multiple sclerosis. We have investigated this concept with a chimeric antagonist anti-human CD40 mAb (ch5D12) in the marmoset monkey experimental autoimmune encephalomyelitis (EAE) model. Marmosets were immunized with recombinant human myelin oligodendrocyte glycoprotein (rMOG) and treated from the day before immunization (day −1) until day 50 with either ch5D12 (5 mg/kg every 2–4 days) or placebo. On day 41 after the induction of EAE, four of four placebo-treated monkeys had developed severe clinical EAE, whereas all animals from the ch5D12-treated group were completely free of disease symptoms. High serum levels of ch5D12 associated with complete coating of CD40 on circulating B cells were found. At necropsy placebo- and ch5D12-treated animals showed similar MOG-specific lymphoproliferative responses in vitro, but ch5D12 treatment resulted in strongly reduced anti-MOG IgM Ab responses and delayed anti-MOG IgG responses. Most importantly, treatment with ch5D12 prevented intramolecular spreading of epitope recognition. Postmortem magnetic resonance imaging and immunohistologic analysis of the CNS showed a markedly reduced lesion load after ch5D12 treatment. In conclusion, the strong reduction of clinical, pathological, and radiological aspects of EAE by ch5D12 treatment in this preclinical model points to a therapeutic potential of this engineered antagonist anti-CD40 mAb for multiple sclerosis.
- Subjects :
- Encephalomyelitis, Autoimmune, Experimental
Time Factors
medicine.drug_class
Recombinant Fusion Proteins
Encephalomyelitis
CD40 Ligand
Immunology
Lymphocyte Activation
Monoclonal antibody
Myelin oligodendrocyte glycoprotein
biology.animal
medicine
Animals
Humans
Immunology and Allergy
CD40 Antigens
B-Lymphocytes
biology
Multiple sclerosis
Experimental autoimmune encephalomyelitis
Antibodies, Monoclonal
Marmoset
Callithrix
medicine.disease
biology.organism_classification
Myelin-Associated Glycoprotein
biology.protein
Immunization
Myelin-Oligodendrocyte Glycoprotein
Antibody
Myelin Proteins
Subjects
Details
- ISSN :
- 00221767
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology, 167, 2942-2949. American Association of Immunologists, Jan Bauer, Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....7e9b2567267664579c772d9be0f7edf6