Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, India.
J Clin Endocrinol Metab. 2012 Sep;97(9):E1820-4. doi: 10.1210/jc.2012-1328. Epub 2012 Jun 20.
The pathogenesis of isolated hypoparathyroidism, also referred to as idiopathic hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation.
We investigated for the association of alleles of the human leukocyte antigen (HLA) class I and II loci with IH.
A total of 134 patients with IH and 902 healthy controls from the same ethnic background participated in the study.
There was a significant increase of HLA class I alleles HLA-A26:01 [P < 1.71 × 10(-34); odds ratio (OR) = 9.29; 95% confidence interval (CI) = 6.08-14.16] and HLA-B08:01 (P < 8.19 × 10(-6); OR = 2.59; 95% CI = 1.63-4.04) in patients with IH compared to healthy controls. However, the association of A26:01 was primary because B08:01 was in linkage disequilibrium with A26:01. Although the major histocompatibility complex (MHC) is very polymorphic, several alleles of HLA loci share key residues at anchor positions in the peptide binding pockets such that similar peptides may be presented by different MHC molecules encoded by the same locus. These allelic forms with similar anchoring amino acids have been clustered in supertypes. An analysis of HLA-A locus supertypes A01, A02, A03, and A04 revealed that supertype A01 was significantly increased (P < 9.18 × 10(-9); OR = 2.95) in IH compared to controls. However, this increase in the supertype A01 was contributed by A26:01 because 68.7% of the A01 samples had A*26:01. Other alleles of the supertype did not show any significant differences.
The strong association of HLA-A*26:01 suggests an important role of MHC class I-mediated presentation of autoantigenic peptides to CD8(+) cytotoxic T cells in the pathogenesis of IH. These data provide evidence for the autoimmune etiology of IH akin to other autoimmune disorders like type 1 diabetes and rheumatoid arthritis.
孤立性甲状旁腺功能减退症（也称为特发性甲状旁腺功能减退症，简称 IH）的发病机制尚不清楚。由于其罕见性，与疾病的免疫遗传基础相关的信息很少。几种自身免疫性疾病的一个反复出现的主题是异常抗原呈递。
我们研究了人类白细胞抗原（HLA）I 类和 II 类基因座的等位基因与 IH 的关联。
共有 134 名 IH 患者和 902 名来自同一种族背景的健康对照者参加了这项研究。
与健康对照组相比，IH 患者中 HLA Ⅰ类等位基因 HLA-A26:01（P＜1.71×10(-34)；优势比（OR）=9.29；95%置信区间（CI）=6.08-14.16）和 HLA-B08:01（P＜8.19×10(-6)；OR=2.59；95%CI=1.63-4.04）显著增加。然而，A26:01 的关联是主要的，因为 B08:01 与 A26:01 呈连锁不平衡。尽管主要组织相容性复合物（MHC）非常多态性，但 HLA 基因座的几个等位基因在肽结合口袋的锚定位点共享关键残基，使得不同 MHC 分子编码的相同基因座可以呈递类似的肽。这些具有相似锚定氨基酸的等位基因形式已聚类为超型。对 HLA-A 基因座超型 A01、A02、A03 和 A04 的分析表明，与对照组相比，IH 中超型 A01 显著增加（P＜9.18×10(-9)；OR=2.95）。然而，A01 超型的这种增加是由 A26:01 引起的，因为 68.7%的 A01 样本具有 A*26:01。该超型的其他等位基因没有显示出任何显著差异。
HLA-A*26:01 的强烈关联表明，MHC Ⅰ类介导的自身抗原肽呈递给 CD8(+)细胞毒性 T 细胞在 IH 的发病机制中起重要作用。这些数据为 IH 的自身免疫病因提供了证据，类似于 1 型糖尿病和类风湿关节炎等其他自身免疫性疾病。
