Pathological and regulatory effects of anti-myelin antibodies in experimental allergic encephalomyelitis in mice

Margaret M Morris-Downes, Paul A Smith, Jon L Rundle, Sara J Piddlesden, David Baker, Danielle Pham-Dinh, Nicole Heijmans, Sandra Amor

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Neurological deficit in experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS) is probably a consequence of synergy between T and B cell responses to CNS antigens. During the demyelinating phase of chronic relapsing EAE in ABH mice, anti-myelin oligodendrocyte glycoprotein (MOG) responses were increased compared to the inflammatory acute phase, but such levels did not correlate with the severity of clinical disease. The pathogenicity of antibodies (Ab) to MOG, myelin basic protein (MBP), proteolipid protein (PLP) and galactocerebroside (GalC) was investigated in vivo following injection at the onset of EAE. An IgG2a monoclonal Ab (mAb), clone Z12, directed to MOG augmented clinical disease and demyelination in ABH and C57BL/6 mice, but not MOG knock-out mice. No effect was observed with F(ab(2))' fragments of Z12 or with the anti-MOG IgG1 mAbs, clones Y10 or 8-18C5. Cobra venom factor partially reduced the augmenting effect of mAb Z12 suggesting a role for complement. The pathogenic effect of anti-myelin Abs was not restricted to MOG since an anti-GalC mAb exacerbated inflammation in the CNS while an MBP mAb (clone 22) reduced clinical disease. Taken together, these data provide further evidence that myelin-reactive Abs generated during autoimmune neurological disease may play an important role not only in the pathogenesis of disease but also the regulation of myelin-targeted autoimmune disease.

Original languageEnglish
Pages (from-to)114-24
Number of pages11
JournalJournal of Neuroimmunology
Volume125
Issue number1-2
Publication statusPublished - Apr 2002

Cite this

Morris-Downes, M. M., Smith, P. A., Rundle, J. L., Piddlesden, S. J., Baker, D., Pham-Dinh, D., ... Amor, S. (2002). Pathological and regulatory effects of anti-myelin antibodies in experimental allergic encephalomyelitis in mice. Journal of Neuroimmunology, 125(1-2), 114-24.