背景:主要组织相容性复合体II类(MHC-II)缺乏症,联合免疫缺陷,来自抗原呈递细胞上II类人类白细胞抗原表达的损失的结果。目前,造血干细胞移植(HSCT)是唯一的治疗方法,尽管影响患者预后的因素仍未得到充分探索。
目的:我们的目的是阐明临床,免疫学,和与MHC-II缺陷相关的遗传特征,并确定影响生存率的预后指标。
方法:在这项多中心回顾性分析中,我们收集了来自土耳其12个中心的35例MHC-II缺乏症患者的数据.我们记录了感染史,基因突变,免疫细胞亚群,和血细胞上的表面MHC-II表达。我们进行了生存分析,以评估各种因素对患者预后的影响。
结果:观察到的主要症状是肺炎(n=29,82.9%),持续性腹泻(n=26,74.3%),和严重感染(n=26,74.3%)。RFXANK基因突变(n=9)最常见,其次是RFX5中的突变(n=8),CIITA(n=4),和RFXAP(n=2)基因。与RFX5突变患者相比,RFXANK突变患者的发病和诊断较晚(分别为p=0.0008和p=0.0006),除了更显著的诊断延迟(p=0.020)。在5例具有特定RFX5突变(c.616G>C)的患者中观察到显著的创始人效应。患者的总生存率为28.6%(n=10),在患有HSCT的个体中显示出明显更高的比例(n=8,80%)。与RFXANK突变患者相比,在具有RFX5突变的患者中观察到早期死亡(p=0.006)和更高的CD8T细胞计数(分别为p=0.006和p=0.009)。
结论:该研究描绘了MHC-II缺乏的遗传和临床全景,强调特定基因突变的流行,如RFXANK和RFX5。这些见解有助于早期诊断和预后完善,显着有助于MHC-II缺乏症的管理。
BACKGROUND: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored.
OBJECTIVE: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates.
METHODS: In this multicenter retrospective analysis, we gathered data from 35 patients with a diagnosis of MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes.
RESULTS: Predominant symptoms observed were pneumonia (n = 29; 82.9%), persistent diarrhea (n = 26; 74.3%), and severe infections (n = 26; 74.3%). The RFXANK gene mutation (n = 9) was the most frequent, followed by mutations in RFX5 (n = 8), CIITA (n = 4), and RFXAP (n = 2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared with those with RFX5 mutations (P =.0008 and .0006, respectively), alongside a more significant diagnostic delay (P = .020). A notable founder effect was observed in five patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n = 10), showing a significantly higher proportion in individuals with hematopoietic stem cell transplantation (n = 8; 80%). Early death and higher CD8+ T-cell counts were observed in patients with the RFX5 mutations compared with RFXANK-mutant patients (P = .006 and .009, respectively).
CONCLUSIONS: This study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency.