Characterization of islet cell antibody in insulin dependent diabetes: evidence for IgG1 subclass restriction and polyclonality.
Using an indirect immunofluorescence technique we have investigated the titre, immunoglobulin class, complement-fixing ability, light chain type and IgG subclass of islet cell antibodies (ICA) in the sera of 21 recently diagnosed insulin-dependent diabetics and four non-diabetics before they developed diabetes. In the recently diagnosed patients titres of ICA ranged from 1/10 to 1/640. ICA belonged to the IgG class in all cases and fixed complement in 14 (67%). In all patients tested both kappa and lambda light chains were found, indicating that the antibody is polyclonal. IgG subclasses of ICA were investigated using specific murine monoclonal antibodies. All patients had ICA of the IgG1 subclass and in 16 (76%) this was the only subclass detected. In the remainder, one or more of the other IgG subclasses were found in association with IgG1. In the four pre-diabetic patients ICA fixed complement, was polyclonal and in all cases was of the IgG1 subclass. These characteristics of ICA, therefore, precede the onset of diabetes. The titre of ICA in the pre-diabetics tended to be greater (range 1/320 to (1/1280) than in the recently diagnosed diabetics. These results demonstrate restriction of ICA to the IgG1 subclass.