Presence of Insulin Autoantibodies as Regular Feature of Nondiabetic Repertoire of Immunity

Abstract

With an ultrasensitive noncompetitive enzyme-linked immunosorbent assay (ELISA), we tested the hypothesis that the presence of insulin autoantibodies in nondiabetic individuals is a normal event. Plasma and peripheral blood mononuclear cells were obtained from 50 nondiabetic whites for determination of insulin autoantibodies by ELISA and radioimmunoassay (anti-insulin IgG [AI-IgG] and 125I-labeled insulin bound [%]), islet cell antibodies, anti-nuclear antibodies and rheumatoid factor, and HLA class II-type antigens (DR, DRw, and DQ). The range of 125I-insulin binding was significantly less than was seen in pretreatment sera from individuals with diabetes (from -0.4 to 0.4% vs. -0.8 to 7.7%, respectively, P = 0.001). Eighty-eight percent of these nondiabetic individuals had significant levels of AI-IgG with preferential binding to human insulin. The geometric mean of AI-IgG concentrations in individuals with significant levels was 180 pM. Binding to human insulin was seen in 88%, to pork insulin in 42%, and to beef insulin in 24% of individuals (P less than 0.001 overall; P less than 0.05 where more bound to pork than beef insulin). Binding of AI-IgG to human insulin-coated plates was substantially inhibited by preincubation with human insulin (median inhibition 57.6%) with little if any inhibition by glucagon, C-peptide, albumin, or IgG. Four individuals had highly specific human AI-IgG as shown by immunoaffinity studies. AI-IgGs were significantly higher in individuals with the HLA haplotype DR4,DRw53,DQ3 and lower in individuals with DR5,DRw52,DQ1 (P = 0.03 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Macroprolactinaemia in patients with hyperprolactinaemia: composition of macroprolactin and stability during long‐term follow‐up

“…Damage to the epitopes or modified antigenicity of iodinated PRL might compromise its ability to bind to anti‐PRL autoantibodies, and sufficient binding might not be achieved under the present experimental conditions. In studies on the binding of autoantibodies to other hormones, the binding ratio for the cut‐off value is also reportedly low; 1·77% for anti‐insulin autoantibodies 25 and 3·9% for anti‐thyroid hormone autoantibodies 26 . Therefore, it might be possible that the proportion of 125 I‐hPRL binding does not reflect the actual levels of autoantibodies.…”

Macroprolactinaemia: prevalence and aetiologies in a large group of hospital workers

“…In addition, dissociation may occur during the binding study. It has been shown in studies of other autoantibodies, such as anti‐insulin autoantibodies 34 and anti‐thyroid hormone autoantibodies, 35 that the binding of iodinated peptides to the autoantibodies is relatively low with a cut‐off point of 1·77% for anti‐insulin autoantibodies and 3·9% for anti‐thyroid hormone autoantibodies. Therefore, it is possible that the ratio of 125 I‐PRL binding actually reflects the ratio of anti‐PRL autoantibodies, but it is underestimated.…”

Insulin autoimmune syndrome: from diagnosis to clinical management

“…IAS is caused by the presence of large amounts of IAA, an autoantibody against insulin in the circulation. IAA can be found in some individuals with an established autoimmunity (53), and in patients with DM-1, especially those who develop the disease at a younger age (54).…”