Experimental allergic neuritis (EAN) as a model for the immune-mediated demyelinating neuropathies.
The inflammatory demyelinating neuropathies (GBS and CIDP) are autoimmune disorders; their pathogenesis and the precise immunological target(s) remain unknown. Valuable insights into the immune mechanisms have been gained from the animal models: Lewis rat EAN and chronic EAN of rabbits. Lewis rats immunized with myelin or myelin proteins P2 and P0 in Freund's adjuvant develop transient paralysis. The pathological findings of nerve edema, perivenular lymphocyte infiltrates and macrophage-mediated demyelination are identical to those of GBS. Severity of clinical EAN and of the pathology correlate with the antigen dose used for immunization. In Lewis rat EAN there is firm evidence of a cell-mediated process. The strongest support for T-cell autoimmunity has come from the adoptive transfer of EAN to syngeneic animals with antigen-specific (P2 and P0) autoreactive T-cells. Humoral factors play a role in the demyelination. Both mechanisms may function synergistically, in that activated neuritogenic T-cells breach the blood-nerve-barrier and thus provide circulating anti-myelin antibodies access to the target tissues. Rabbits immunized with a single large multiportal dose of myelin predictably develop EAN with a chronic progressive or relapsing course. The clinical, electrophysiological and pathological features are identical to human CIDP. IgM and IgG anti-Gal C antibody titres parallel the disease course and have demyelinating activity. T-cell responses have not yet been characterized in this model. Both forms of EAN lend themselves to the study of very specific immunotherapies.
Hahn
A F
AF
University of Western Ontario, Victoria Hospital, London, Canada.
D000818:Animals; D001327:Autoimmune Diseases; D003711:Demyelinating Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew