Strong association of insulin autoimmune syndrome with HLA-DR4.
case_control · Level III
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Abstract
Insulin autoimmune syndrome is characterised by spontaneous hypoglycaemia without evidence of exogenous insulin administration, a high serum concentration of total immunoreactive insulin, and the presence of insulin autoantibodies in high titre. HLA typing of 27 patients with insulin autoimmune syndrome showed that all had DR4, which was present in only 43% of 51 healthy controls (odds ratio 72.1, p less than 2 x 10(-6), and 19 (70%) of the patients were positive for the allelic combination, Cw4, Bw62, and DR4. Analysis of the nucleotide sequences of the DRB1, DQA1, and DQB1 genes showed that all the patients had DRB1*0406, DQA1*0301, and DQB1*0302, compared with only 14% of the controls (odds ratio 281, p less than 1 x 10(-10). We conclude that the development of insulin autoimmune syndrome is associated with a strong genetic predisposition.