Glutamic acid decarboxylase autoantibody prevalence and association with HLA genotype in patients with younger-onset type 1 diabetes and proliferative diabetic retinopathy.
OBJECTIVE
To investigate the relationship of HLA status and autoantibodies to glutamic acid decarboxylase (GAD) in proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity and genetic markers in retinopathy.


METHODS
Retrospective, nonrandomized, comparative study.


METHODS
Patients who had suffered from type 1 diabetes for >10 years and who had been first diagnosed as diabetic under 30 years of age were studied. They were classified into 3 groups: 20 patients with diabetes and PDR (PDR group), 22 patients who had diabetes and severe nonproliferative diabetic retinopathy (SNPDR group), and 25 patients who had diabetes with no diabetic retinopathy (non-DR group).


METHODS
Blood was collected, and the relationship between HLA status and GAD autoantibody positivity in diabetic retinopathy was investigated in a cross-sectional study.


METHODS
Human leukocyte antigen status and GAD autoantibody positivity.


RESULTS
The highest positive rate of GAD autoantibody was 56.0% in the non-DR group, followed by the SNPDR group (40.1%) and the PDR group (15.0%). The frequencies of the HLA-DQ4 and -DR4/-DQ4 haplotypes were significantly higher in the PDR group (75.0% and 65%, respectively) than in the SNPDR group (40.9% and 31.8%) or the non-DR group (40.0% and 28.0%) (P = 0.035 and P = 0.026, respectively). The prevalence of GAD antibodies was lower in patients with the HLA-DR4 and HLA-DQ4 alleles and -DR4/-DQ4 haplotype frequencies in the PDR group (P = 0.018, P = 0.0088, and P = 0.0031, respectively).


CONCLUSIONS
We found that the existence of GAD antibodies is inversely related and HLA status is directly related to the stage or severity of retinopathy.
Mimura
Tatsuya
T
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114-2500, USA. mimurat-tky@umin.ac.jp
Funatsu
Hideharu
H
Uchigata
Yasuko
Y
Kitano
Shigehiko
S
Shimizu
Erika
E
Amano
Shiro
S
Yamagami
Satoru
S
Noma
Hidetaka
H
Araie
Makoto
M
Hori
Sadao
S
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D003601:Cytotoxicity Tests, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D015995:Prevalence; D011863:Radioimmunoassay
D001323:Autoantibodies; D005819:Genetic Markers; D006681:HLA-D Antigens; D005968:Glutamate Decarboxylase