Presence of insulin autoantibodies as regular feature of nondiabetic repertoire of immunity

Diabetes. 1991 Sep;40(9):1187-93. doi: 10.2337/diab.40.9.1187.

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)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Autoantibodies / analysis*
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HLA-D Antigens / analysis*
  • HLA-DQ Antigens / analysis
  • HLA-DR Antigens / analysis
  • Humans
  • Immunoglobulin G / analysis
  • Insulin / immunology*
  • Insulin Antibodies / analysis*
  • Male
  • Radioimmunoassay
  • Reference Values

Substances

  • Autoantibodies
  • HLA-D Antigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Immunoglobulin G
  • Insulin
  • Insulin Antibodies