Immunology Department, National Institute of Pediatrics, Mexico City, Mexico.
Research Unit for Immunodeficiencies, National Institute of Pediatrics, 1 Iman Avenue, Floor 9, 04530, Mexico City, Mexico.
J Clin Immunol. 2023 Jan;43(1):123-135. doi: 10.1007/s10875-022-01357-8. Epub 2022 Aug 31.
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rβ1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.
孟德尔易感性分枝杆菌病 (MSMD) 是一种罕见的遗传疾病，其特征为对细胞内病原体（如分枝杆菌、减毒牛分枝杆菌卡介苗（BCG）疫苗株和环境分枝杆菌）的免疫受损，这些病原体在其他健康个体中存在。回顾性研究综述了墨西哥 MSMD 患者的临床、免疫学和遗传学特征。总体而言，2006 年至 2021 年期间共纳入了 22 名诊断为 MSMD 的患者：14 名男性（64%）和 8 名女性。12 名患者（70%）在接种 BCG 后发生了 BCG 感染。此外，有 6 名患者（22%）发生了细菌性感染，主要由沙门氏菌引起，如下文所述，还发生了真菌感染，特别是组织胞浆菌。7 名患者死于播散性 BCG 病。在 IL12RB1（n=13）、IFNGR1（n=3）和 IFNGR2（n=1）基因中鉴定出了 13 种不同的致病性变异体。白细胞介素-12Rβ1 缺陷是本队列中 MSMD 的主要原因。发病率和死亡率主要归因于 BCG 感染。
