Kuhlen Michaela, Hönscheid Andrea, Loizou Loizos, Nabhani Schafiq, Fischer Ute, Stepensky Polina, Schaper Jörg, Klapper Wolfram, Siepermann Meinolf, Schuster Friedhelm, Meisel Roland, Borkhardt Arndt
University of Duesseldorf, Medical Faculty, Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Duesseldorf, Germany.
Pediatric Oncology-Hematology Clinic, Archbishop Makarios III Hospital, Nicosia, Cyprus.
Clin Immunol. 2016 Jan;162:27-30. doi: 10.1016/j.clim.2015.10.008. Epub 2015 Oct 31.
PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1) gain-of-function has recently been described in patients with recurrent sinopulmonary infections, chronic CMV-/EBV-infections, lymphoproliferation, and hypogammaglobulinemia. Here we report a 15-year-old boy with treatment refractory CMV lymphadenitis, severe combined immunodeficiency, microcephaly and a severe developmental defect of Th17 cells. To avoid poor outcome, hematopoietic stem cell transplantation (HSCT) was performed. Subsequently, whole exome sequencing revealed a de novo heterozygous G-to-C mutation (chr5: 5:67,589,663: G>C) at the splice donor site of the PIK3R1 gene. Our data suggest that PIK3R1 gain-of-function leads to developmental defects in helper and regulatory T-cell subsets, the latter expanding the immunological features of PIK3R1 gain-of-function. T-cell subsets play a critical role in the regulation of immune response against infectious agents and of autoimmunity and thus may be particularly accountable for the clinical phenotype of affected patients.
PIK3R1（磷脂酰肌醇-3-激酶调节亚基1）功能获得性突变最近在患有复发性鼻窦肺部感染、慢性巨细胞病毒/EB病毒感染、淋巴细胞增殖和低丙种球蛋白血症的患者中被发现。在此，我们报告一名15岁男孩，患有治疗难治性巨细胞病毒淋巴结炎、严重联合免疫缺陷、小头畸形以及Th17细胞严重发育缺陷。为避免不良后果，进行了造血干细胞移植（HSCT）。随后，全外显子组测序在PIK3R1基因的剪接供体位点发现了一个新生的杂合G到C突变（chr5: 5:67,589,663: G>C）。我们的数据表明，PIK3R1功能获得性突变导致辅助性和调节性T细胞亚群发育缺陷，后者扩展了PIK3R1功能获得性突变的免疫特征。T细胞亚群在针对感染因子的免疫反应调节和自身免疫中起关键作用，因此可能是受影响患者临床表型的特别原因。
