Division of Allergy and Clinical Immunology, Department of Pediatrics, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de La Santé Et de La Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.
J Clin Immunol. 2023 Nov;43(8):1941-1952. doi: 10.1007/s10875-023-01562-z. Epub 2023 Aug 16.
Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy.
We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency.
Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died.
MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population.
主要组织相容性复合体 II 类（MHC-II）缺陷是一种罕见的先天性免疫缺陷（IEI）。抗原呈递给 CD4+T 细胞的能力受损会导致联合免疫缺陷（CID）。患者通常在早期出现严重的呼吸道和胃肠道感染。造血干细胞移植（HSCT）是唯一的治愈性治疗方法。
我们描述了 18 名伊朗 MHC-II 缺陷无关患者的临床、免疫和遗传特征。
所有受影响的家庭都有近亲结婚。首次就诊时的中位年龄为 5.5 个月（范围 7 天至 18 岁）。主要症状包括生长发育不良、持续腹泻和肺炎。约三分之一的患者还记录了自身免疫和神经系统特征。13 名患者携带 RFXANK 基因突变，2 名患者携带 RFX5 基因突变，3 名患者携带 RFXAP 基因突变。6 名患者携带相同的 RFXANK 启动子突变（c.162delG）；仅在伊朗人群中发现，可追溯到大约 1296 年前。其中 4 名患者接受了 HSCT；其中 3 名患者存活。另一方面，未接受 HSCT 的 14 名患者中有 9 名预后不良并死亡。
MHC-II 缺陷在伊朗并不罕见，近亲结婚率高。在任何年龄，都应将其作为 CID 的鉴别诊断。由于 HSCT 可及性有限且在 MHC-II 缺陷中的结果各不相同，因此必须为受影响的家庭提供遗传咨询和计划生育。我们更有决心研究伊朗人群中 c.162delG RFXANK 杂合突变的频率。
