Laboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School, São Paulo, Brazil.
J Clin Immunol. 2012 Aug;32(4):778-85. doi: 10.1007/s10875-012-9673-4. Epub 2012 Mar 9.
The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes (T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives.
IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM.
Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes.
The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.
本研究旨在确定巴西 1 型糖尿病（T1DM）患者一级亲属中异质性胰岛细胞细胞质自身抗体（ICA）、谷氨酸脱羧酶（65）（GAD（65）A）、胰岛素瘤相关抗原-2（IA-2A）和胰岛素（IAA）及人类白细胞抗原（HLA）Ⅱ类标志物（HLA-DR 和 -DQ）的频率。本研究的一个主要重点是确定年龄、性别、先证者特征和家族史对自身抗体和 HLA-DR 和 -DQ 等位基因流行率的影响，以及这些因素对一级亲属中 T1DM 发病和遗传易感性的影响。
在 178 例 T1DM 巴西患者的 546 名一级亲属、244 名兄弟姐妹、55 名子女和 233 名父母中，测定了 IAA、ICA、GAD（65）A、IA-2A 和 HLA-Ⅱ类等位基因。
总的来说，8.9%的亲属存在一种或多种自身抗体阳性。父母中仅检测到 IAA 抗体。与父母相比，GAD（65）是子女和兄弟姐妹中最常见的抗体，也是子女中唯一检测到的抗体。有 5 名兄弟姐妹对 IA-2 抗体呈阳性。有相当数量（62.1%）的兄弟姐妹具有 1 或 2 个高风险 HLA 单倍型。在 4 年的随访研究中，5 名兄弟姐妹（表达 HLA-DR3 或 -DR4 等位基因）和 1 名 GAD（65）A 阳性的子女进展为糖尿病。
数据表明，在我们的研究人群中，GAD（65）和 IA-2 抗体是 T1DM 的最强预测因子。高风险 HLA 单倍型本身并不能预测进展为显性糖尿病。
