[Insulin antibodies: methodology and clinical implications]

Abstract

Anti-insulin antibodies detection is based on the demonstration of a specific and saturable binding to insulin either radiolabelled with 125 I (Radiobinding assay or RBA) or coated on a solid phase (Enzyme linked immunosorbent assay or EIA). The 2 assays are remarkably different by their sensitivity to the affinity of the antigen antibody reaction. In addition, RBA may be biased by the presence of the iodine atom on the radioiodinated insulin whereas, at least on theoretical grounds. EIA could be biased because of denaturation or non availability of some epitopes when insulin is coated. Anti-insulin antibodies may be induced by insulin therapy. When they "spontaneously" appear, they are called autoantibodies. Insulin autoantibodies may be detected in the normal population, in type 1 diabetic patients before any administration of exogenous insulin and in patients suffering from the autoimmune hypoglycemic syndrome. In some patients, this syndrome may be associated with administration of a thiol containing drug. In some cases, insulin antibodies may appear several years after a transient insulin therapy, possibly as a consequence of a disturbance of the immunologic memory. The properties of antibodies and autoantibodies (concentration, affinity, number and nature of epitopes, heavy and light chain composition and ability to form aggregates) are relatively characteristic of the disease with which they are associated and determine their potential effects on insulin bioavailability and plasma glucose homeostasis.