Comparison of insulin autoantibodies in diabetes-related and healthy populations by precise displacement ELISA.
The second international workshop on insulin autoantibodies (IAAs) demonstrated improved concordance among laboratories with both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) when measurements were based on signals displaceable by preincubation with excess insulin. This feature has been incorporated into our original ELISA for IAAs, and the assay was used to compare IAAs in diabetes-related and healthy populations. The serum from a healthy islet cell antibody (ICA)+ and IAA+ subject was used to construct standard curves with and without preincubation with 1 U/ml human insulin. Reporting results in arbitrary displacement (delta +/- IAA) units derived from the standard curve improved precision and increased the specificity of the assay. Frequency analysis of the results from 200 control adults did not show a normal distribution, and cumulative frequency analysis demonstrated two populations: 10 of 200 (5%) control adults, 8 of 241 (3.3%) healthy schoolchildren, and 18 of 229 (7.9%) non-insulin-dependent diabetes mellitus (NIDDM) patients had IAAs greater than 12 delta +/- IAA units. On the same basis, we tested samples from 89 individuals in the prospective Bart's Windsor Family Study for insulin-dependent diabetes mellitus (IDDM), 31 of whom had ICAs greater than 5 Juvenile Diabetes Foundation (JDF) units. Of those with ICAs greater than 5 JDF units, 12 developed IDDM and 1 developed NIDDM in 10 yr of study. IAAs greater than 12 delta +/- IAA units were found in 6 of 12 (50%) who became diabetic and in 4 of 18 (22%) who remain healthy.(ABSTRACT TRUNCATED AT 250 WORDS)
Dean
B M
BM
Department of Immunology, University College and Middlesex School of Medicine, London, UK.
McNally
J M
JM
Bonifacio
E
E
Jennings
A M
AM
Dunger
D B
DB
Gale
E A
EA
Bottazzo
G F
GF
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D002648:Child; D003920:Diabetes Mellitus / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007330:Insulin Antibodies / Q000032:analysis*; D007515:Islets of Langerhans / Q000276:immunology; D012016:Reference Values
D001323:Autoantibodies; D015415:Biomarkers; D007330:Insulin Antibodies; C024211:islet cell antibody