Clinical and genetic characteristics of diabetic patients with high-titer (>10,000 U/ml) of antibodies to glutamic acid decarboxylase.

Abstract	We investigated the clinical aspects and genetic background of 13 diabetic patients with high-titers (>10,000 U/ml) of anti-glutamic acid decarboxylase antibody (Group A) and compared these 28 middle-aged (35-51 years, Group B) and 13 elderly (66-79 years, Group C) patients with anti-GAD(+) (<1100 U/ml) who were diagnosed initially as having type 2 diabetes. The mean age and mean age at onset of Group A were 70.8 +/- 3.9 years (range, 64-78) and 50.4 +/- 5.4 years (range, 43-61), respectively. In Group A, the prevalence of insulin-deficient patients was significantly lower (30.8%, 4 of 13) than in Group C (96.3%, 27 of 28, P < 0.001). Patients in Group A had a significantly longer interval between the clinical onset of diabetes to initiation insulin therapy (21.8 +/- 2.3 years) compared to patients in both Group B (1.8+/-1.1 years, P < 0.001) and Group C (14.8 +/- 7.1 years, P = 0.049). The frequency of DRB10405-DQB10401/DRB11502-DQB10601 or DRB1501-DQB0602 heterozygous genotypes in Group A (53.8%, 7 of 13) was significantly higher than in both Group B (3.6%, 1 of 28, P < 0.01) and Group C (7.7%, 1 of 13, P < 0.05). Compared with Group B, Group A had an increased frequency of the TNFA-U01 haplotype and the IL-10 -592 C allele (TNFA-U01; 53.8% versus 30.4%, P = 0.05 and IL-10 -592 C; 57.7% versus 33.9 %, P = 0.042). All sera from Group A reacted with GAD(65) protein on Western blots. We conclude that adult-onset diabetic patients with a high-titer of anti-GDAab differ from patients with latent autoimmune diabetes mellitus in adult (LADA) with respect to beta-cell function, cellular autoimmunity and genetic background. Our study also showed that high-titers of antibodies to glutamic acid decarboxylase (anti-GADab) were not predictive of later development of insulin deficiency in adult and/or elderly patients with type 2 diabetes. Furthermore, our results suggest that HLA-DRB11502-DQB10601 or DRB11501-DQB10602/DRB10405-DQB10401 heterozygous genotypes may be associated with high production of anti-GADab that recognizes the linear epitope(s) on the GAD(65) protein.
Authors	Michiyo Ishii, Goji Hasegawa, Michiaki Fukui, Hiroshi Obayashi, Mitsuhiro Ohta, Masakazu Ogata, Keiji Yoshioka, Yoshihiro Kitagawa, Koji Nakano, Toshikazu Yoshikawa, Naoto Nakamura
Journal	Immunology letters (Immunol Lett) Vol. 99 Issue 2 Pg. 180-5 (Jul 15 2005) ISSN: 0165-2478 [Print] Netherlands
PMID	16009268 (Publication Type: Comparative Study, Journal Article)
Chemical References	Autoantibodies HLA-DQ Antigens HLA-DR Antigens HLA-DRB1 Chains Insulin Glutamate Decarboxylase
Topics	Adult Age of Onset Aged Autoantibodies (blood, immunology) Diabetes Mellitus, Type 1 (enzymology, genetics, immunology) Diabetes Mellitus, Type 2 (enzymology, genetics, immunology) Female Glutamate Decarboxylase (immunology) HLA-DQ Antigens (genetics) HLA-DR Antigens (genetics) HLA-DRB1 Chains Haplotypes Heterozygote Humans Insulin (therapeutic use) Japan Longitudinal Studies Male Middle Aged Polymerase Chain Reaction

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