Patients with Graves' disease who developed insulin autoimmune syndrome (Hirata disease) possess HLA-Bw62/Cw4/DR4 carrying DRB1*0406.
The insulin autoimmune syndrome (IAS) is characterized by the following diagnostic criteria: severe spontaneous hypoglycemia without evidence of exogenous insulin administration, high levels of total serum immunoreactive insulin, and the presence of a high titer of antiinsulin antibody. Just before the onset of IAS, 13 of the 35 (37%) patients with IAS examined in this study had taken methimazole for the treatment of Graves' disease. To investigate the difference between the Graves' disease patients treated with methimazole who developed IAS and other IAS patients, HLA class II genes in both groups were analyzed by serological and DNA typing methods. All 13 patients with Graves' disease who developed IAS possessed a specific allelic combination, Bw62/Cw4/DR4 carrying DRB1*0406, whereas only 1 of 50 Graves' disease patients without IAS had Bw62/Cw4/DR4 (odds ratio, 891; P < 1 x 10(-10)) and carried not DRB1*0406 (odds ratio, 2727; P < 1 x 10(-10)), but DRB1*0405. Of the 22 IAS patients without Graves' disease, 13 had the combination Bw62/Cw4/DR4 carrying DRB1*0406 (odds ratio, 19.0; P < 0.07). Thus, it is highly likely that patients with Graves' disease develop IAS via treatment with methimazole when their Bw62/Cw4/DR4 carry DRB1*0406.
Uchigata
Y
Y
Diabetes Center, Tokyo Women's Medical College, Japan.
Kuwata
S
S
Tsushima
T
T
Tokunaga
K
K
Miyamoto
M
M
Tsuchikawa
K
K
Hirata
Y
Y
Juji
T
T
Omori
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D006111:Graves Disease / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D015235:HLA-B Antigens / Q000032:analysis / Q000235:genetics; D059910:HLA-B15 Antigen; D015236:HLA-C Antigens / Q000032:analysis / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000032:analysis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000276:immunology*; D007330:Insulin Antibodies / Q000097:blood; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D015235:HLA-B Antigens; D059910:HLA-B15 Antigen; C044141:HLA-Bw62; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D007330:Insulin Antibodies; D008713:Methimazole; D004247:DNA