Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2215-e2227. doi: 10.1210/clinem/dgab038.
Despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism.
This work aimed to evaluate immune function in hypoparathyroidism.
The Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control, cross-sectional study set in an Italian referral center. Participants included 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measures included calcium metabolism assessment, peripheral blood mononuclear cells (PBMC) profiling via flow cytometry, parathyroid hormone receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time polymerase chain reaction, cytokine measurement, and evaluation of infectious disease frequency and severity.
Immune cell profiling revealed decreased monocytes, regulatory, naive, and total CD4+ T lymphocytes, which correlated with total calcium, ionized calcium, and PTH levels, in patients with hypoparathyroidism. Patients with hypoparathyroidism had a higher CD3-CD56+ natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor gene expression and decreased circulating TNF levels. Gene expression and immunofluorescence analysis confirmed PTHr1 expression in all PBMC lineages; however, the percentage of cells expressing PTHr1 was lower, whereas the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8+CD4+ and CD4+ T lymphocytes, and total NK cells was higher in patients with hypoparathyroidism.
This study describes for the first time the immune alterations in patients with hypoparathyroidism receiving conventional therapies, supporting the immunoregulatory role of PTH and proposing an explanation for the increased susceptibility to infections observed in epidemiological studies.
尽管钙信号在免疫反应中起着关键作用，但人们对甲状旁腺功能减退症患者的免疫功能知之甚少。
本研究旨在评估甲状旁腺功能减退症患者的免疫功能。
术后和自身免疫性甲状旁腺功能减退症的免疫功能评估（NCT04059380）是一项在意大利转诊中心进行的病例对照、横断面研究。参与者包括 20 例术后甲状旁腺功能减退症患者（12 名女性）和 20 名年龄和性别匹配的对照者。主要观察指标包括钙代谢评估、通过流式细胞术对外周血单个核细胞（PBMC）进行分析、使用免疫荧光和 PrimeFlow RNA 检测甲状旁腺激素受体 1（PTHr1）表达分析、通过实时聚合酶链反应进行基因表达分析、细胞因子测量以及评估传染病的频率和严重程度。
免疫细胞分析显示，甲状旁腺功能减退症患者的单核细胞、调节性、幼稚和总 CD4+T 淋巴细胞减少，与总钙、离子钙和 PTH 水平相关。甲状旁腺功能减退症患者的 CD3-CD56+自然杀伤（NK）细胞计数较高，与钙、PTH 和维生素 D 水平呈负相关。此外，他们表现出肿瘤坏死因子（TNF）和粒细胞-巨噬细胞集落刺激因子基因表达减少，以及循环 TNF 水平降低。基因表达和免疫荧光分析证实所有 PBMC 谱系均表达 PTHr1；然而，甲状旁腺功能减退症患者的 PTHr1 表达细胞百分比较低，而单核细胞、总 T 淋巴细胞、CD8+CD4+和 CD4+T 淋巴细胞以及总 NK 细胞中 PTHr1 表达的强度较高。
本研究首次描述了接受常规治疗的甲状旁腺功能减退症患者的免疫改变，支持 PTH 的免疫调节作用，并为流行病学研究中观察到的感染易感性增加提供了一种解释。
