Complement-mediated cytotoxic effects of islet cell surface antibodies in non-diabetic subjects with antecedent mumps infection and diabetic risk.
We studied sera of 24 selected non-diabetic subjects in whom an antecedent mumps infection with either complications and/or with onset at older age occurred 10-27 month ago regarding the capability to lyse rat islets of Langerhans in vitro. Thirteen subjects were characterized by diabetes associated HLA antigens DR3 and/or DR4 whereas 11 of them had none of these HLA antigens. Islet cell surface antibodies (ICSA) could be detected in 11 out of 24 subjects. Isolated pancreatic islets from 8-10 days old Wistar rats were incubated in freshly prepared human serum. The insulin leakage under the conditions of pharmacologic blockade of insulin secretion by means of epinephrine and propranolol provides a measure of complement-mediated cytotoxicity of human serum against rats islets in vitro. Out of a total of 24 subjects the sera of 11 of them exhibited cytotoxicity. Mean cytolytic insulin leakage was significantly higher in subjects with DR3 and/or DR4 in comparison with subjects without these HLA antigens (6.82 +/- 0.77% vs 3.90 +/- 0.48%; p less than 0.05). Ten out of the 11 subjects with cytotoxic sera had HLA DR3 and/or DR4 whereas DR3 was present in three out of 13 subjects with non-cytotoxic sera. There was no relationship between beta cell function in vivo (fasting C-peptide concentration and insulin response to oral glucose challenge) and the capability of patients sera to damage islet cells in vitro. In conclusion the pathogenetic role of mumps virus and cytotoxic ICSA and their possible relation to slow progressive beta-cell destruction has still to be ascertained.
D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002648:Child; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009107:Mumps / Q000097:blood / Q000150:complications*; D051381:Rats; D011919:Rats, Inbred Strains
D000906:Antibodies; D007328:Insulin