GAD - 65 and IA - 2 Autoantibodies in Relation to HLA Class II DR and DQ 3 Alleles and Haplotypes in Type 1 Diabetes Mellitus
نویسندگان
چکیده
26 Background. The frequency of autoantibodies against glutamic acid decarboxylase-65 27 (GAD65), and ICA512/IA2 (IA2) are a function of the specific human leukocyte antigen 28 (HLA) in type 1 diabetes mellitus (T1D). We investigated the association of HLA class II 29 (DR, DQ) alleles and haplotypes with the presence of GAD and IA-2 autoantibodies in T1D. 30 Methods. Autoantibodies were tested in 88 Tunisian T1D patients and 112 age-and gender31 matched normoglycemic control subjects by enzyme immunoassay. 32 Results. Among T1D patients, mean anti-GAD antibody titers were higher in DRB1*030101 33 allele (P <0.001), together with DRB1*030101/DQB1*0201 (P <0.001) and 34 DRB1*040101/DQB1*0302 (P = 0.002) haplotypes, while lower anti-GAD titers were 35 associated with DRB1*070101 (P = 0.001) and DRB1*110101 (P < 0.001) alleles, and 36 DRB1*070101/DQB1*0201 (P = 0.001) and DRB1*110101/DQB1*030101 (P = 0.001) 37 haplotypes. Mean anti-IA2 antibody titers were higher in DRB1*040101 allele (P = 0.007) 38 and DRB1*040101/DQB1*0302 (P = 0.001) haplotypes, but were lower in DRB1*110101 39 allele (P = 0.010) and DRB1*110101 (P < 0.001), and DRB1*110101/DQB1*030101 (P = 40 0.025) haplotype. Multinomial regression analysis confirmed positive association of 41 DRB1*030101, and negative association of DRB1*110101 and DQB1*030101, along with 42 DRB1*070101/DQB1*0201 and DRB1*110101/DQB1*030101 haplotypes with anti-GAD 43 levels. By contrast, only DRB1*040101/DQB1*0302 haplotype was positively associated 44 with altered anti-IA2 titers. 45 Conclusion. Increased GAD65and IA-2-Abs positivity is differentially associated with 46 select HLA class II alleles and haplotypes, confirming the heterogeneous nature of T1D. 47 48
منابع مشابه
Evidence That HLA Class I and II Associations With Type 1 Diabetes, Autoantibodies to GAD and Autoantibodies to IA-2, Are Distinct
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