Abstract

Mutations in the interleukin-21 receptor (IL-21R) gene are recently defined as primary immunodeficiency diseases. IL-21R defects result in combined immunodeficiency by affecting the functions of innate and adaptive immune system components.

A six-year-old girl was admitted to our hospital with complaints of chronic diarrhea that started after the newborn period and generalized rash over the last three months. She had severe respiratory distress due to Cytomegalovirus (CMV) pneumonia requiring mechanical ventilation and was diagnosed as combined immunodeficiency at another hospital at the age of four. Her physical examination on admission revealed erythematous rash on cheeks, extremities, gluteal region, and lymph node enlargements in cervical, axillary, and inguinal regions. CMV DNA and stool Cryptosporidium parvum were positive. Marginal zone lymphoma –negative for Epstein-Bar virus– was reported in the lymph node biopsy. Targeted next-generation sequencing Ion AmpliSeq™ primary immunodeficiency panel revealed a novel homozygous IL21R c.132delC (p.Ser45fs) mutation.

This case is presented to emphasize that IL21R defects should be considered in the differential diagnosis of the patients with recurrent respiratory infections, chronic diarrhea, C. parvum infection, chronic liver disease, sclerosing cholangitis, and malignancy where early hematopoietic stem cell transplantation (HSCT) is life-saving. A total of eight cases with IL21R gene defects have been reported so far. The significance of this case is that it is the first case of malignancy among the published IL-21R deficient patients successfully treated with HSCT.

摘要

白细胞介素 21 受体 (IL-21R) 基因的突变最近被定义为原发性免疫缺陷疾病。IL-21R 缺陷通过影响先天性和适应性免疫系统成分的功能而导致联合免疫缺陷。

一名 6 岁女孩因在新生儿期后开始出现慢性腹泻和过去三个月出现全身皮疹而入院。她因需要机械通气的巨细胞病毒 (CMV) 肺炎而出现严重的呼吸窘迫，4 岁时在另一家医院被诊断为联合免疫缺陷。入院时的体格检查显示，脸颊、四肢、臀区有红斑，颈部、腋窝和腹股沟区淋巴结肿大。CMV DNA 和粪便隐孢子虫是积极的。淋巴结活检报告了边缘区淋巴瘤（Epstein-Bar 病毒阴性）。靶向二代测序 Ion AmpliSeq™ 原发性免疫缺陷 panel 揭示了一种新的纯合 IL21R c.132delC (p.Ser45fs) 突变。

该病例旨在强调IL21R缺陷在反复呼吸道感染、慢性腹泻、细小梭菌感染、慢性肝病、硬化性胆管炎和早期造血干细胞移植（HSCT）的恶性肿瘤患者的鉴别诊断中应予以考虑。是救命的。迄今为止，共报道了8例IL21R基因缺陷病例。该病例的意义在于，它是已发表的IL-21R缺陷患者中首例通过HSCT成功治疗的恶性肿瘤。