Chronic experimental autoimmune encephalomyelitis. Circulating autoantibodies bind predominantly determinants expressed by complexes of basic protein and lipids of myelin.
Chronic relapsing experimental autoimmune encephalomyelitis (CREAE) was induced by immunising juvenile strain 13 guinea pigs with homologous spinal cord tissue in adjuvant. Thirteen animals were killed in the early chronic (5-12 weeks post immunisation) and 8 in the late chronic phase (after 15 weeks pi). Plasma titres of antibodies to an isolated myelin preparation were determined by enzyme linked immunoassay. Elevated titres of these antibodies were detected between 5-26 weeks pi, varied by 10-fold between different individuals, and had no direct relationship to clinical status or time pi. Of 20 CREAE plasma with anti-myelin immunoglobulins (Igs), only 3 contained substantial amounts of antibodies to myelin lipid and these were all from animals in the late chronic phase. By contrast 15/20 of the samples contained antibodies which appeared to require lipid-protein interactions for optimal binding to antigens in isolated myelin. There was a close correlation between plasma titres of antibodies to isolated myelin and to purified myelin basic protein (MBP). Even in samples with a moderately high lipid requirement for binding to isolated myelin, purified MBP could inhibit at least 50% of the binding. These observations suggest that MBP-lipid complexes are dominant immunogens in CREAE. Gross inflammation and myelin loss in spinal cords from these CREAE guinea pigs were determined by light microscopy. Substantial inflammation was apparent in some animals between 7 and 26 weeks pi. The most severe myelin loss was observed in late chronic phase animals having plasma anti-myelin Igs with a variety of specificities. The data suggest that circulating antibodies to myelin lipids or MBP-lipid complexes could contribute to demyelination in CREAE but their titres do not correlate with the extent of this process.
P
P
Glynn
D
D
Weedon
M L
ML
Cuzner
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D055598:Chemical Phenomena; D002621:Chemistry; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006168:Guinea Pigs; D008055:Lipids / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D008055:Lipids; D004676:Myelin Basic Protein