Department of Allergy and Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
J Clin Immunol. 2019 Aug;39(6):600-610. doi: 10.1007/s10875-019-00672-x. Epub 2019 Jul 31.
Although many studies have investigated Mendelian susceptibility to mycobacterial disease (MSMD) worldwide, there is no report of the long-term clinical management and prognosis for MSMD in China.
This is a cohort study from January 2000 to June 2018. Three hundred and twenty-four patients with bacillus Calmette-Guérin (BCG) infection were diagnosed during this period, and those with MSMD diagnosed by genetic and functional experiments were enrolled in the study. The clinical and genetic characteristics and management of these MSMD patients were summarized.
Thirty patients diagnosed with MSMD were followed up. The age at the follow-up end point ranged from 5 to 173 months. Among the patients, IL12RB1 mutations were identified in 22, IFNGR1 mutations in 5, STAT1 mutations in 2, and IFNGR2 mutation in 1. The medium age at onset was 3 months. BCG infection involved multiple organs, including regional infection (8/30; 26.7%) or distant or disseminated infection (22/30; 73.3%). Ten percent (30/324) of patients with BCG infection had a confirmed MSMD diagnosis. Protein expression of IL12RB1 or IFNGR1 was decreased in all patients with IL12RB1 or IFNGR1 mutation, respectively, as indicated by flow cytometry. In addition, 77.8% of patients received rhIFN-γ treatment, which can improve the prognosis of patients with IL12RB1 deficiency. Two patients received stem cell transplantation. Twenty-five patients remained alive at the time of publication.
MSMD is an important cause of BCG infection. Flow cytometric detection of IL12RB1 and IFNGR1 expression is very useful for rapid MSMD diagnosis. rhIFN-γ therapy is effective in patients with MSMD, particularly improving prognosis in those with IL12RB1 deficiency.
尽管世界各地已有许多研究调查了分枝杆菌病的孟德尔易感性（MSMD），但在中国尚无 MSMD 长期临床管理和预后的报告。
这是一项 2000 年 1 月至 2018 年 6 月的队列研究。在此期间，诊断了 324 例卡介苗（BCG）感染者，对通过遗传和功能实验诊断为 MSMD 的患者进行了研究。总结了这些 MSMD 患者的临床和遗传特征以及管理情况。
对 30 例确诊为 MSMD 的患者进行了随访。随访终点的年龄范围为 5 至 173 个月。其中，22 例患者存在 IL12RB1 突变，5 例患者存在 IFNGR1 突变，2 例患者存在 STAT1 突变，1 例患者存在 IFNGR2 突变。发病的中位年龄为 3 个月。BCG 感染累及多个器官，包括局部感染（8/30；26.7%）或远处或播散性感染（22/30；73.3%）。324 例 BCG 感染者中有 10%（30 例）确诊为 MSMD。所有 IL12RB1 或 IFNGR1 突变患者的 IL12RB1 或 IFNGR1 蛋白表达均降低，流式细胞术也证实了这一点。此外，77.8%的患者接受了 rhIFN-γ 治疗，这可以改善 IL12RB1 缺陷患者的预后。有 2 例患者接受了干细胞移植。在发表时，25 例患者仍然存活。
MSMD 是 BCG 感染的重要原因。IL12RB1 和 IFNGR1 表达的流式细胞术检测对快速诊断 MSMD 非常有用。rhIFN-γ 治疗对 MSMD 患者有效，特别是改善了 IL12RB1 缺陷患者的预后。
