Islet cell surface antibodies from insulin-dependent diabetics bind specifically to pancreatic B cells.
Viable rat islet cells were used to detect islet cell surface antibodies (ICSA) in the sera of diabetic and control patients. ICSA were present in almost all recent-onset insulin-dependent diabetics younger than 30 yr (15/16); their incidence in other diabetics (6/22) was also higher than in normal controls (1/18) or in patients with autoimmune thyroiditis (1/12). The varying specificity of the ICSA for the different islet cell types led to the recognition of class I sera, whose ICSA bind exclusively to B cells, class II sera, binding only to A and pancreatic polypeptide (PP) cells and class III sera, reacting with the three islet cell types but not with D cells. Most recent-onset insulin-dependent diabetics younger than 30 contained class I-ICSA, which is consistent with an autoimmune basis of their disease and with an involvement of surface antibodies in the B cell destruction. The presence of class II ICSA in three older diabetics and in one normal control raises the question whether autoimmune reactions against A and PP cells exist and are associated with a distinct entity in islet disease. It is concluded that the autoimmune form of diabetes mellitus represents a heterogeneous group, in which ICSA-positive patients can be distinguished on the basis of their ICSA-binding to one or more islet cell types. Three techniques can be used for the further identification of circulating ICSA, namely binding experiments with purified A or B cells, electron microscopical analysis of ICSA-binding islet cells purified by fluorescence-activated cell sorting, and the immunocytochemical characterization of ICSA-positive cells.
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001666:Binding Sites, Antibody; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000032:analysis; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D010191:Pancreatic Polypeptide / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin; D011965:Receptors, Glucocorticoid; D013004:Somatostatin / Q000032:analysis; D013966:Thyroiditis / Q000276:immunology
D001323:Autoantibodies; D011965:Receptors, Glucocorticoid; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D011972:Receptor, Insulin