Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, Pisa, Italy.
Department of Medicine of Laboratory, Section of Cytogenetics, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Clin Exp Immunol. 2020 Jun;200(3):272-286. doi: 10.1111/cei.13429. Epub 2020 Apr 16.
22q11.2 deletion syndrome (22q11.2DS) is characterized by a heterogeneous phenotype, including alterations in phospho-calcium metabolism and immunodeficiency. We analyzed vitamin D status and the immune assessment, focusing on T cell subpopulations and dendritic cells (DCs) in a cohort of 17 pediatric 22q11.2DS patients and 17 age-matched healthy subjects. As antigen-presenting cells, DCs are the main target of vitamin D, promoting a tolerogenic T cell response. Patients were subdivided into three groups according to the parameters of phospho-calcium metabolism and serum levels of 25OHD: normal values, vitamin D deficiency and hypoparathyroidism. Different degrees of T cell deficiency, ranging from normal to partial T cell numbers, were observed in the cohort of patients. The group with vitamin D deficiency showed a significant reduction of naive T cells and a significant increase of central memory T cells compared to controls. In this group the number of circulating DCs was significantly reduced. DC decrease affected both myeloid and plasmacytoid DC subsets (mDCs and pDCs), with the most relevant reduction involving pDCs. A direct correlation between 25OHD levels and recent thymic emigrant (RTE) and DC number was identified. Despite the limited cohort analyzed, our results show that deficiency of the pDC subset in patients with 22q11.2DS may be included among the causative factors of the progressive increase of risk of autoimmune diseases in these patients. As most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, we suggest a potential role of vitamin D supplementation in preventing autoimmune or proinflammatory diseases in 22q11.2DS.
22q11.2 缺失综合征(22q11.2DS)的表型具有异质性,包括磷酸钙代谢和免疫缺陷的改变。我们分析了维生素 D 状态和免疫评估,重点是 T 细胞亚群和树突状细胞(DCs),该研究纳入了 17 名儿科 22q11.2DS 患者和 17 名年龄匹配的健康对照。作为抗原呈递细胞,DCs 是维生素 D 的主要靶标,促进耐受的 T 细胞反应。根据磷酸钙代谢和血清 25OHD 水平的参数,患者被分为三组:正常值、维生素 D 缺乏和甲状旁腺功能减退症。在患者队列中观察到不同程度的 T 细胞缺陷,从正常到部分 T 细胞数量减少。与对照组相比,维生素 D 缺乏组的幼稚 T 细胞显著减少,中央记忆 T 细胞显著增加。在该组中,循环 DC 数量显著减少。DC 减少影响髓样和浆细胞样 DC 亚群(mDCs 和 pDCs),其中最相关的减少涉及 pDCs。25OHD 水平与近期胸腺迁出细胞(RTE)和 DC 数量之间存在直接相关性。尽管分析的患者队列有限,但我们的结果表明,22q11.2DS 患者中 pDC 亚群的缺乏可能是这些患者自身免疫性疾病风险增加的原因之一。由于大多数患者易患感染增加和自身免疫性疾病的患病率升高,我们建议在 22q11.2DS 中补充维生素 D 可能有助于预防自身免疫或炎症性疾病。