a Section of Medical Pathophysiology, Center of Rare Diseases, Department of Experimental Medicine , Sapienza University of Rome , Rome , Italy.
Autoimmunity. 2018 Jun;51(4):175-182. doi: 10.1080/08916934.2018.1477134. Epub 2018 Jun 28.
In literature, the importance of X-linked gene dosage as a contributing factor for autoimmune diseases is generally assumed. However, little information is available on the frequency of humoral endocrine organ-specific autoimmunity in X-chromosome aneuploidies. In our preliminary study, we investigated the endocrine organ-specific humoral autoimmunity relative to four different organ-specific autoimmune diseases in a group of adult 47,XXY KS patients and in adults 46,XY control males (type 1 diabetes, T1DM; Addison's disease, AD; Hashimoto thyroiditis, HT; autoimmune chronic atrophic gastritis, AG). The aim of the present study is to evaluate the frequency of autoantibodies (Abs) specific for T1DM, AD, HT, and AG in rarer higher grade X-chromosome aneuploidies (HGA) and in 47,XXY children.
Samples from 192 Caucasian patients with an X-chromosome aneuploidy (176 patients (55 children, 121 adults) with 47,XXY karyotype (KS patients) and 16 HGA patients (eight children, eight adults)) recruited from Sapienza, University of Rome (2007-2017) were tested for Abs specific for T1DM (insulin-Abs, GAD-Abs, IA-2-Abs, Znt8-Abs), HT (TPO-Abs), AD (21-OH-Abs), and AG (APC-Abs). The results were compared to those found in 213 46,XY control subjects (96 children, 117 adults).
Altogether humoral organ-specific immunoreactivity was found in 13% of KS and HGA patients, with a significantly higher frequency than in the controls (p=.008). Almost 19% of HGA patients were positive for at least one of the organ-specific Abs investigated compared to 12.5% of KS patients. The frequency of the overall immunoreactivity was higher in KS children than in KS adults. The frequency of diabetes-specific Abs was significantly higher in the patient cohort than in controls (p=.005). Thyroid- and gastric-specific autoimmunity was also found in KS and HGA patients, while adrenal-specific immunoreactivity was rare.
These results suggest for the first time that the risk of endocrine organ-specific humoral autoimmunity progressively increases with the severity of X-chromosome polisomy. The screening for diabetes-, thyroid-, and gastric-specific autoimmunity should be considered in clinical practice for identifying rare and classic X-chromosome aneuploid patients at risk of developing organ-specific autoimmune diseases.
在文献中，X 连锁基因剂量作为自身免疫性疾病的一个致病因素的重要性通常被认为是确定的。然而，关于 X 染色体非整倍体中体液内分泌器官特异性自身免疫的频率，信息很少。在我们的初步研究中，我们调查了一组成年 47，XXY KS 患者和成年 46，XY 对照男性（1 型糖尿病、T1DM；Addison 病、AD；桥本甲状腺炎、HT；自身免疫性慢性萎缩性胃炎、AG）中与四种不同器官特异性自身免疫性疾病相关的内分泌器官特异性体液自身免疫。本研究的目的是评估在更罕见的高级别 X 染色体非整倍体（HGA）和 47，XXY 儿童中，针对 T1DM、AD、HT 和 AG 的自身抗体（Abs）的频率。
从罗马萨皮恩扎大学（2007-2017 年）招募的 192 名 X 染色体非整倍体患者（176 名患者（55 名儿童，121 名成人）具有 47，XXY 核型（KS 患者）和 16 名 HGA 患者（8 名儿童，8 名成人））的样本进行了针对 T1DM（胰岛素-Abs、GAD-Abs、IA-2-Abs、Znt8-Abs）、HT（TPO-Abs）、AD（21-OH-Abs）和 AG（APC-Abs）的特异性 Abs 检测。将结果与 213 名 46，XY 对照受试者（96 名儿童，117 名成人）的结果进行了比较。
共有 13%的 KS 和 HGA 患者出现体液器官特异性免疫反应，明显高于对照组（p=.008）。与 12.5%的 KS 患者相比，近 19%的 HGA 患者至少有一种所研究的器官特异性 Abs 呈阳性。KS 儿童的整体免疫反应频率高于 KS 成人。患者组中糖尿病特异性 Abs 的频率明显高于对照组（p=.005）。KS 和 HGA 患者也发现了甲状腺和胃特异性自身免疫，而肾上腺特异性免疫反应很少见。
这些结果首次表明，X 染色体三体的严重程度与内分泌器官特异性体液自身免疫的风险呈正相关。在临床实践中，应考虑对糖尿病、甲状腺和胃特异性自身免疫进行筛查，以识别有发生器官特异性自身免疫性疾病风险的罕见和经典 X 染色体非整倍体患者。
