Presence of insulin autoantibodies as regular feature of nondiabetic repertoire of immunity.
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)
Fineberg
S E
SE
Department of Medicine, Indiana University, Indianapolis.
Biegel
A A
AA
Durr
K L
KL
Hufferd
S
S
Fineberg
N S
NS
Anderson
J H
JH
D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006681:HLA-D Antigens / Q000032:analysis*; D006683:HLA-DQ Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007328:Insulin / Q000276:immunology*; D007330:Insulin Antibodies / Q000032:analysis*; D008297:Male; D011863:Radioimmunoassay; D012016:Reference Values
D001323:Autoantibodies; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies