Hyperacute autoimmune encephalomyelitis induced by a synthetic autoantigen

Abstract

EXPERIMENTAL autoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease of the central nervous system (CNS) induced by immunisation with CNS tissue in complete Freund's adjuvant (CFA). It is generally regarded as an animal model of acute disseminated encephalomyelitis. In Lewis rats a hyperacute variant of EAE can be induced using appropriate CNS immunogen with Bordetella pertussis vaccine as adjuvant with or without CFA^1–3. Hyperacute EAE (HEAE) differs from ordinary EAE clinically in its early onset and in its rapid and severe course, with high incidence of cerebral involvement and mortality. Histological lesions of HEAE are characterised by the presence in the CNS parenchyma of polymorphonuclear leukocytes, and necrosis, haemorrhage, oedema and fibrin^1,2. Because HEAE and ordinary EAE overlap histopathologically and immunologically² they provide experimental evidence supporting the concept that certain human demyelinating diseases represent a spectrum of autoimmunity ranging from chronic multiple sclerosis to acute haemorrhagic necrotising leukoencephalopathy, for which HEAE is a model^1,2,4. We report here that the induction of HEAE is favoured by the absence of a methyl group in a sequence of 14 amino acids of the primary structure of the immunogen.