Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN), Av. I.P.N. 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico.
Research Department, Hospital Regional "Licenciado Adolfo López Mateos", ISSSTE, Av. Universidad 1321, Florida, 01030, Mexico City, Mexico.
Acta Diabetol. 2018 Dec;55(12):1275-1282. doi: 10.1007/s00592-018-1241-9. Epub 2018 Oct 10.
To assess the prevalence of autoantibodies (Aab) to insulin (IAA), glutamic acid decarboxylase 65 (GADA) and insulinoma antigen 2 (IA-2A), as well as human leukocyte antigen (HLA) class II alleles, in first degree relatives (FDR) of Mexican patients with type 1 diabetes (T1D), and to explore whether these parameters mirror the low incidence of T1D in the Mexican population.
Aab titers were determined by ELISA in 425 FDR, 234 siblings, 40 offspring and 151 parents of 197 patients with T1D. Typing of HLA-DR and -DQ alleles was performed in 41 Aab-positive FDR using polymerase chain reaction with allele-specific oligotyping.
Seventy FDR (16.47%) tested positive for Aab. The siblings (19.2%) and the offspring (25%) had significantly higher prevalence of Aab than the parents (9.9%). GADA was the most frequent Aab. Almost half of the Aab-positive FDR had two different Aab (45.7%), and none tested positive for three Aab. The highest prevalence of Aab was found among women in the 15-29 years age group. Moreover, the positivity for two Aab was significantly more frequent among females. A considerable number of FDR (48.8%) carried the susceptible HLA-DR3, -DR4, -DQB10201 or -DQB10302 alleles, but almost none had the high risk genotype HLA-DR3/DR4.
FDR of Mexican T1D patients have high prevalence of islet Aab, comparable to countries with the highest incidence of T1D. However, Aab positivity does not seem to be associated with HLA risk genotypes, which may have an impact on the low incidence of T1D in Mexico.
评估墨西哥 1 型糖尿病(T1D)患者一级亲属(FDR)中抗胰岛素(IAA)、谷氨酸脱羧酶 65(GADA)和胰岛素瘤抗原 2(IA-2A)自身抗体(Aab)以及人类白细胞抗原(HLA)II 类等位基因的流行率,并探讨这些参数是否反映了墨西哥人群中 T1D 的低发病率。
通过 ELISA 法检测了 197 例 T1D 患者的 425 名 FDR、234 名兄弟姐妹、40 名子女和 151 名父母的 Aab 滴度。采用聚合酶链反应与等位基因特异性寡核苷酸分型对 41 名 Aab 阳性 FDR 进行 HLA-DR 和 -DQ 等位基因分型。
70 名 FDR(16.47%)检测出 Aab 阳性。兄弟姐妹(19.2%)和子女(25%)的 Aab 阳性率明显高于父母(9.9%)。GADA 是最常见的 Aab。近一半的 Aab 阳性 FDR 有两种不同的 Aab(45.7%),没有一种检测出三种 Aab 阳性。15-29 岁年龄组女性 Aab 阳性率最高。此外,女性中两种 Aab 阳性的比例明显更高。相当一部分 FDR(48.8%)携带易感 HLA-DR3、-DR4、-DQB10201 或 -DQB10302 等位基因,但几乎没有高风险基因型 HLA-DR3/DR4。
墨西哥 T1D 患者的 FDR 存在胰岛 Aab 的高流行率,与 T1D 发病率最高的国家相当。然而,Aab 阳性似乎与 HLA 风险基因型无关,这可能对墨西哥 T1D 的低发病率有影响。