Association between HLA and islet cell antibodies in diabetic patients with a mitochondrial DNA mutation at base pair 3243.
Islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxylase (GAD) and HLA genotypes were examined in 31 patients with diabetes and a mitochondrial gene mutation located at base pair 3243 (mtDNA 3243 mutation). ICA was detected in 42% (13/31) of these patients compared to 0 of 90 among healthy control subjects. The ICA showed a "non-restricted" pattern of staining in all 13 ICA-positive patients. In a sensitive radioligand assay only 2 of 31 (6%) diabetic patients with the mutation were positive for both GAD65 autoantibodies and ICA, while the remaining 29 patients were GAD65 antibody negative. The ICA-positive patients had an increased frequency of the HLA-DQA1*0301 allele compared to control subjects (p < 0.05). Of the diabetic patients with the mutation 45% (14/31) had progressive clinical course of beta-cell failure. These results indicate that patients with an mtDNA 3243 mutation may develop islet autoimmunity associated with ICA and GAD autoantibodies. We hypothesize that the presence of HLA-DQA1*0301 in individuals with the mtDNA 3243 mutation increases the risk for diabetes and associated autoantibodies against islet cell antigens.
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
T
T
Kobayashi
Y
Y
Oka
H
H
Katagiri
A
A
Falorni
A
A
Kasuga
I
I
Takei
K
K
Nakanishi
T
T
Murase
K
K
Kosaka
A
A
Lernmark
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012016:Reference Values; D012307:Risk Factors
D001323:Autoantibodies; D004272:DNA, Mitochondrial; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; C024211:islet cell antibody; D005968:Glutamate Decarboxylase