Anti-GAD65 autoantibody in Taiwanese patients with insulin-dependent diabetes mellitus: effect of HLA on anti-GAD65 positivity and clinical characteristics.
OBJECTIVE
Anti-GAD65 antibody has been studied widely in patients with insulin-dependent diabetes mellitus (IDDM) in many different populations. However, the prevalence of GAD65 autoantibody has not been assessed in Taiwanese patients with IDDM. We therefore characterized GAD65 antibody and investigated the effect of HLA-DR phenotypes on GAD65 autoimmunity and other clinical characteristics in Taiwanese subjects with IDDM.


METHODS
Two hundred and twenty-five patients (male 102, female 123) with IDDM were recruited. The diagnostic criteria for IDDM were age of onset before 30 years, presence of diabetic ketoacidosis, and insulin-dependency within 3 years of onset. We employed a radioligand method to detect GAD65 antibody. HLA-DR typing was performed by the PCR-SSO techniques. Plasma C-peptide and anti-thyroid microsomal antibody were also measured.


RESULTS
The prevalence of GAD65 antibody according to duration of disease were 50/91 (54.9%), 37/95 (38.9%), 8/24 (33%), and 3/15 (20%) among the groups of duration < or = 5, 6-10, 11-15, and > 15 years, respectively (p = 0.0011). There were no significant differences between GAD(+) and GAD(-) patients in age of onset (11.5 +/- 6.5 and 11.6 +/- 13.4 years, respectively), gender distribution (male:female 39:59 and 58:69, respectively) and percentage with residual beta cell function (38.8% and 29.1%, respectively). Multiple regression analysis revealed that duration of IDDM correlated inversely with residual beta cell function. Earlier onset of IDDM correlated with a loss of beta cell function and a HLA-DR phenotype containing DR3/4, DR3/3 or DR3/9.


CONCLUSIONS
Prevalence of GAD65 autoantibody among Taiwanese subjects with IDDM was negatively correlated with duration of disease. Different determinants in the HLA-DR locus contributed to the clinical onset of IDDM but not to GAD autoimmunity.
Chuang
L M
LM
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei.
Lin
C Y
CY
Wu
H P
HP
Tsai
W Y
WY
Tai
T Y
TY
Lin
B J
BJ
D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D016130:Immunophenotyping; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D015995:Prevalence; D012044:Regression Analysis; D013624:Taiwan; D013997:Time Factors
D001323:Autoantibodies; D001324:Autoantigens; D002096:C-Peptide; D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen; D059811:HLA-DRB1 Chains; C056626:thyroid microsomal antibodies; D005968:Glutamate Decarboxylase