Department of Pediatrics, Allergy-Immunology and Pediatric Rheumatology Division, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
Curr Allergy Asthma Rep. 2018 Jun 23;18(8):44. doi: 10.1007/s11882-018-0797-3.
Many genetic conditions predispose affected individuals to opportunistic infections. A number of immunodeficiency diseases, including genetic defects termed Mendelian susceptibility to mycobacterial disease (MSMD), permit infection from many different strains of mycobacteria that would otherwise not cause disease. These include tuberculous and nontuberculous mycobacteria, and bacille Calmette-Guérin vaccine (BCG). Patients may present with infections from other organisms that depend on macrophage function for containment. Defects in multiple genes in the IL-12 and NFKB signaling pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1.
Multiple autosomal recessive and dominant, and 2 X-linked recessive gene defects resulting in the MSMD phenotype have been reported, and others await discovery. This review presents the known gene defects and describes clinical findings that result from the mutations. If MSMD is suspected, a careful clinical history and examination and basic immunodeficiency screening tests will narrow the differential diagnosis. A specific diagnosis requires more sophisticated laboratory investigation. Genetic testing permits a definitive diagnosis, permitting genetic counseling. Mild cases respond well to appropriate antibiotic therapy, whereas severe disease may require hematopoietic stem cell transplantation.
许多遗传条件使受影响的个体易患机会性感染。许多免疫缺陷疾病，包括被称为“孟德尔易感性分枝杆菌病（MSMD）”的遗传缺陷，允许感染许多不同株的分枝杆菌，否则这些分枝杆菌不会引起疾病。这些包括结核分枝杆菌和非结核分枝杆菌，以及卡介苗（BCG）。患者可能会出现依赖于巨噬细胞功能进行控制的其他生物体感染。白细胞介素 12（IL-12）和 NF-κB 信号通路中的多个基因缺陷可导致 MSMD 表型，其中一些包括 IL12RB1、IL12B、IKBKG、ISG15、IFNGR1、IFNGR2、CYBB、TYK2、IRF8 和 STAT1。
已报道多种常染色体隐性和显性以及 2 种 X 连锁隐性基因缺陷导致 MSMD 表型，还有其他缺陷有待发现。本综述介绍了已知的基因缺陷，并描述了由突变引起的临床发现。如果怀疑 MSMD，仔细的临床病史和检查以及基本免疫缺陷筛查试验将缩小鉴别诊断范围。特定诊断需要更复杂的实验室检查。遗传检测可做出明确诊断，从而进行遗传咨询。轻度病例对适当的抗生素治疗反应良好，而严重疾病可能需要造血干细胞移植。
