Panimolle Francesca, Tiberti Claudio, Granato Simona, Semeraro Antonella, Gianfrilli Daniele, Anzuini Antonella, Lenzi Andrea, Radicioni Antonio
Section of Medical Pathophysiology, Department of Experimental Medicine, Center of Rare Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
Endocrine. 2016 Apr;52(1):157-64. doi: 10.1007/s12020-015-0613-y. Epub 2015 May 3.
The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter's syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison's disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM.
本研究的目的是通过调查1型糖尿病（T1DM）、艾迪生病（AD）、桥本甲状腺炎（HT）和自身免疫性慢性萎缩性胃炎（AG）特异性自身抗体谱，评估47,XXY克氏综合征（KS）患者体液内分泌器官特异性自身免疫的频率。对61名成年白种人47,XXY KS患者进行了T1DM特异性自身抗体（胰岛素抗体、谷氨酸脱羧酶抗体、胰岛抗原2抗体、锌转运体8抗体）、HT（甲状腺过氧化物酶抗体）、AD（21-羟化酶抗体）和AG（胃蛋白酶原抗体）检测。其中35例患者未接受睾酮替代治疗（TRT）（第1组），其余26例患者在研究开始前开始接受TRT（第2组）。将KS患者自身抗体频率与122名对照男性的频率进行比较。61例KS患者中有6例（9.8%）至少一种内分泌自身抗体呈阳性，而对照组为6.5%。有趣的是，KS内分泌免疫反应主要针对糖尿病特异性自身抗原（8.2%），其频率显著高于对照组（p = 0.016）。2例KS患者（3.3%）甲状腺过氧化物酶抗体呈阳性，而没有患者AD和AG相关自身抗原呈阳性。未治疗和治疗的KS患者自身抗体内分泌谱无显著差异。我们的研究首次表明，内分泌体液免疫反应在KS患者中并不罕见，且更频繁地针对1型糖尿病相关自身抗原，因此提示在临床实践中筛查器官特异性自身免疫的重要性。需要进行随访研究以确定自身抗体阳性的KS患者是否会发展为临床T1DM。
