Lum Su Han, Neven Benedicte, Slatter Mary A, Gennery Andrew R
Children's Haematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
Paris Descartes-Sorbonne Paris Cité University, Paris, France.
Front Pediatr. 2019 Dec 11;7:516. doi: 10.3389/fped.2019.00516. eCollection 2019.
Major histocompatibility complex (MHC) class II deficiency is a rare and fatal primary combined immunodeficiency. It affects both marrow-derived cells and thymic epithelium, leading to impaired antigen presentation by antigen presenting cells and delayed and incomplete maturation of CD4+ lymphocyte populations. Affected children are susceptible to multiple infections by viruses, , bacteria and fungi. Immunological assessment usually shows severe CD4+ T-lymphocytopenia, hypogammaglobulinemia, and lack of antigen-specific antibody responses. The diagnosis is confirmed by absence of constitutive and inducible expression of MHC class II molecules on affected cell types which is the immunologic hallmark of the disease. Hematopoietic cell transplantation (HCT) is the only established curative therapy for MHC class II deficiency but it is difficult as affected children have significant comorbidities at the time of HCT. Optimization organ function, implementing a reduced toxicity conditioning regimen, improved T-cell depletion techniques using serotherapy and graft manipulation, vigilant infection surveillance, pre-emptive and aggressive therapy for infection and newer treatments for graft-versus-host disease have improved the transplant survival for children with MHC class II deficiency. Despite persistent low CD4+ T-lymphopenia reported in post-HCT patients, transplanted patients show normalization of antigen-specific T-lymphocyte stimulation and antibody production in response to immunization antigens. There is a need for a multi-center collaborative study to look at transplant survival of HCT and long-term disease outcome in children with MHC class II deficiency in the modern era of HCT.
主要组织相容性复合体（MHC）II类缺陷是一种罕见且致命的原发性联合免疫缺陷病。它影响骨髓来源的细胞和胸腺上皮，导致抗原呈递细胞的抗原呈递受损以及CD4 +淋巴细胞群体成熟延迟和不完全。患病儿童易受病毒、细菌和真菌的多种感染。免疫评估通常显示严重的CD4 + T淋巴细胞减少、低丙种球蛋白血症以及缺乏抗原特异性抗体反应。通过在受影响的细胞类型上缺乏MHC II类分子的组成性和诱导性表达来确诊，这是该疾病的免疫学标志。造血细胞移植（HCT）是MHC II类缺陷唯一已确立的治愈性疗法，但由于患病儿童在进行HCT时存在严重的合并症，所以难度较大。优化器官功能、实施降低毒性的预处理方案、使用血清疗法和移植物操作改进T细胞清除技术、警惕感染监测、对感染进行抢先和积极治疗以及针对移植物抗宿主病的新疗法，都提高了MHC II类缺陷儿童的移植存活率。尽管移植后患者报告持续存在低CD4 + T淋巴细胞减少，但移植患者对抗免疫抗原的抗原特异性T淋巴细胞刺激和抗体产生显示正常化。在现代造血细胞移植时代，需要进行多中心合作研究，以观察MHC II类缺陷儿童的造血细胞移植存活率和长期疾病结局。
