Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody.
We postulated that humoral autoimmunity can play a beneficial role in CNS demyelinating diseases such as multiple sclerosis. We previously demonstrated that monoclonal natural autoantibody SCH94.03 suppresses CNS inflammation and promotes remyelination in a virus-induced model of chronic progressive multiple sclerosis. To further investigate the relationship between natural autoimmunity and CNS demyelination, we examined the effect of SCH94.03 treatment on clinical relapses and pathological disease in SJL/J mice with established adoptive-transfer relapsing experimental autoimmune encephalomyelitis. Treatment with SCH94.03 after recovery from the initial episode of clinical disease reduced relapse rates by half, prolonged relapse onset by 6 days and reduced spinal cord demyelination and meningeal inflammation by 40%. These results are consistent with the hypothesized immunomodulatory function of natural autoantibodies, and are the first direct demonstration that natural humoral autoimmunity can be beneficial in an autoimmune T-cell-mediated CNS demyelinating disease.
Miller
D J
DJ
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Bright
J J
JJ
Sriram
S
S
Rodriguez
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001323:Autoantibodies / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy*; D005260:Female; D007075:Immunoglobulin M / Q000627:therapeutic use; D007167:Immunotherapy; D051379:Mice; D008815:Mice, Inbred Strains; D012008:Recurrence; D013116:Spinal Cord / Q000473:pathology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007075:Immunoglobulin M; C101676:SCH94.03 monoclonal antibody