Heterogeneity in the specificity of the islet cell cytoplasmic antibody response in insulin-dependent diabetes mellitus.
We assessed the heterogeneity in the islet cell cytoplasmic antibody (ICA) response of insulin-dependent diabetes mellitus (IDDM) patients via indirect immunofluorescence on frozen sections of human, bovine, and porcine pancreas. The three substrates detected comparable frequencies of ICA positives among the IDDM sera tested, whereas control sera were ICA negative on all three substrates. However, individual IDDM serum samples showed heterogeneity in ICA binding on the three pancreata. Of 28 sera tested on all three substrates, 22 were ICA positive on human pancreas, three were ICA positive on bovine pancreas, and two were ICA positive on porcine pancreas. Sensitivity of ICA epitopes to neuraminidase treatment and periodate oxidation suggests that glycoconjugates are recognized by serum ICA. Cholera toxin blocked ICA binding. However, the functional cholera toxin receptor ganglioside Gm1 is resistant to neuraminidase treatment and periodate oxidation. Therefore, it is unlikely that Gm1 is the ICA determinant. These data suggest that not all ICA antigens are equivalently expressed on islets from different pancreata and/or that each individual responds to a hierarchy of islet antigens such that restricted patterns of specific ICA binding are found.
Kawahara
D J
DJ
Diabetes Research Laboratory, Childrens Hospital of Orange County, California 92668.
Buckingham
B
B
Kershnar
A
A
D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology* / Q000502:physiology; D000917:Antibody Formation / Q000276:immunology* / Q000502:physiology; D000918:Antibody Specificity / Q000276:immunology* / Q000502:physiology; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects; D001894:Borohydrides / Q000494:pharmacology; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D009439:Neuraminidase / Q000494:pharmacology; D010084:Oxidation-Reduction; D010179:Pancreas / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010504:Periodic Acid / Q000494:pharmacology; D013045:Species Specificity; D013552:Swine
D000910:Antibodies, Heterophile; D001323:Autoantibodies; D001894:Borohydrides; D000939:Epitopes; D006001:Glycoconjugates; C024211:islet cell antibody; D010504:Periodic Acid; D002772:Cholera Toxin; D009439:Neuraminidase