title: Characterization of adrenal autoantigens recognized by sera from patients with autoimmune polyglandular syndrome (APS) type I.
abstract: Steroidogenic enzymes P450scc, P450c17 and P450c21 have recently been shown to be the main autoantigens recognized by sera from patients with autoimmune polyglandular syndrome (APS type I) with or without Addison's disease. We have studied the interrelationships of autoantigens revealed with APS type I sera in the adrenal and in placenta by immunodiffusion and immunoblotting, and correlated the findings to reactivities towards the above steroidogenic enzymes. We studied 50 patients with APS type I, 36 of whom also had Addison's disease, three patients with isolated (adult type) Addison's disease, seven healthy relatives of the patients with APS type I, 18 patients with insulin-dependent diabetes mellitus, 17 patients with autoimmune liver disease and 26 healthy controls. Immunodiffusion revealed two precipitating autoantigens in adrenal gland, and one of these was also found in placenta. In immunoblotting, five major adrenal antigens with molecular sizes of 55 kDa, 48 kDa, 43 kDa, 39 kDa and 19 kDa were seen. Reactivity to the 55 kDa, 39 kDa or 19 kDa represents the occurrence of antibodies to P450c17 or to its components as revealed by comparative studies with mouse antibodies to recombinant P450c17. These three bands in immunoblot as well as precipitating antibodies were observed exclusively in APS type I patients who had or developed Addison's disease. The 48 kDa antigen was found also in placenta and is probably P450scc, judged by the high correlation of P450scc antibodies with immunodiffusion and immunoblotting results using placental homogenate. There was no association between reactivity to the 43 kDa band and other immune parameters studied. The results thus indicate that P450scc and P450c17 enzymes are the precipitating adrenal autoantigens recognized by sera from APS type I patients. However, according to immunoblot results there could be some yet unidentified adrenal autoantigens to which APS type I patients could develop antibodies.
authors.affiliation: Institute of Biomedical Sciences, University of Tampere, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Uibo
authors.forename: J
authors.initials: J
authors.lastname: Perheentupa
authors.forename: V
authors.initials: V
authors.lastname: Ovod
authors.forename: K J
authors.initials: KJ
authors.lastname: Krohn
mesh_terms: D000224:Addison Disease / Q000150:complications / Q000276:immunology; D000311:Adrenal Glands / Q000201:enzymology / Q000276:immunology*; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000032:analysis*; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D005779:Immunodiffusion; D008107:Liver Diseases / Q000150:complications / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D010920:Placenta / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System