title: Circulating immune complexes may play a regulatory and pathogenic role in experimental autoimmune uveoretinitis.
abstract: We compared the time course of changes in serum levels of circulating immune complexes (CICs) and of IgG antibody after sensitization of albino Lewis and pigmented Lister strain rats with uveitogenic (retinal S-antigen) and non-uveitogenic (ovalbumin) protein antigens of comparable molecular weight. Normal levels of CICs were far lower in Lewis rats in which experimental autoimmune uveoretinitis (EAU) takes the form of a severe panuveitis, than in Lister rats, in which the disease is mild, focal, confined to the posterior segment, and of lower incidence. After sensitization with either S-antigen or ovalbumin, polyethylene-glycol-precipitable CIC (PEG-CIC) peaked and fell as IgG antibody levels rose in both rat strains. However, peak levels of PEG-CIC were lower and subsequent IgG antibody levels were higher in the Lewis strain than in the less susceptible Lister strain. In both strains of rat these linked PEG-CIC/IgG antibody responses occurred earlier after sensitization with uveitogenic (S-) antigen than with ovalbumin, whether or not individual S-antigen-sensitized Lister rats developed EAU. In contrast, complement-binding CIC rose substantially only in those rats of both strains displaying EAU in response to S-antigen and not in response to ovalbumin. We suggest that immune complex (idiotypic) regulation of IgG antibody responses may be more readily perturbed by a pathogenic autoantigen (S-antigen) than by a bland antigen (ovalbumin). We also suggest that differences between the balance of regulatory and pathogenic CIC responses to uveitogenic retinal antigen may underlie or reflect strain differences in susceptibility to and severity of EAU.
authors.affiliation: Department of Immunology, United Medical School, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Kasp
authors.forename: M R
authors.initials: MR
authors.lastname: Stanford
authors.forename: E
authors.initials: E
authors.lastname: Brown
authors.forename: A G
authors.initials: AG
authors.lastname: Coombes
authors.forename: D C
authors.initials: DC
authors.lastname: Dumonde
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood / Q000502:physiology*; D000941:Antigens / Q000276:immunology; D019393:Arrestin; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology; D005620:Freund's Adjuvant; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000276:immunology* / Q000473:pathology; D013045:Species Specificity; D014605:Uveitis / Q000276:immunology* / Q000473:pathology
chemical_list: D000936:Antigen-Antibody Complex; D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D007074:Immunoglobulin G; D010047:Ovalbumin; D005620:Freund's Adjuvant