Glutamic acid decarboxylase autoantibody prevalence and association with HLA genotype in patients with younger-onset type 1 diabetes and proliferative diabetic retinopathy

Ophthalmology. 2005 Nov;112(11):1904-9. doi: 10.1016/j.ophtha.2005.05.016. Epub 2005 Sep 12.

Abstract

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.

Design: Retrospective, nonrandomized, comparative study.

Participants: 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.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoantibodies / blood*
  • Autoimmunity
  • Cytotoxicity Tests, Immunologic
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetic Retinopathy / genetics*
  • Diabetic Retinopathy / immunology*
  • Female
  • Genetic Markers
  • Genotype
  • Glutamate Decarboxylase / immunology*
  • HLA-D Antigens / genetics*
  • Histocompatibility Testing
  • Humans
  • Male
  • Prevalence
  • Radioimmunoassay

Substances

  • Autoantibodies
  • Genetic Markers
  • HLA-D Antigens
  • Glutamate Decarboxylase