Polymorphism of insulin antibodies in six patients with insulin-immune hypoglycaemic syndrome

Abstract

Insulin antibodies in six patients with immune hypoglycaemic syndrome were studied. The antibodies displayed a higher affinity for bovine insulin in two patients, were specific for human insulin in one patient and non-species specific in the other three patients. The predominant IgG subclass of the insulin antibodies was IgG4 in two patients, IgG3 in two and IgG1 in two. In one of these, the other three subclasses were also detectable. Insulin autoantibodies of four patients were homogeneous with regard to light chains (kappa), and those of the other two contained both kappa and gamma light chains. Analysis of insulin immune complex size by fast protein liquid chromatography was possible in three patients and demonstrated immune complexes with elution profile close to that of IgG, although not exactly superimposable to the one obtained with a mouse monoclonal insulin antibody. In two patients, avidity was too low to permit chromatography of the immune complexes, and, moreover, in these two cases insulin antibodies were of the IgG3 isotype and spontaneously formed aggregates independently of insulin binding. We conclude that insulin antibodies of the insulin immune syndrome are polymorphic but different from those generated by insulin therapy.