Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease - A review of 17 patients living in a region endemic for tuberculosis
Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease - A review of 17 patients living in a region endemic for tuberculosis
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DOI：
10.1097/inf.0b013e31815b494c
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发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Lau, Yu-Lung
中科院分区：
文献类型：
--
作者：
Lee, Pamela P. W.;Chan, Koon-Wing;Lau, Yu-Lung
背景：慢性肉芽肿病(CGD)是一种罕见的吞噬细胞氧化爆发的疾病，导致反复的化脓性感染。金黄色葡萄球菌、沙门氏菌、念珠菌和曲霉菌感染是本中心儿童感染的主要致病因素。目的：了解X-连锁CGD患者的感染谱，重点分析本中心发现的所有CyB13基因突变。结果：1988-2005年间，17例中国男性儿童确诊为X-连锁CGD。共检测到15个突变，包括3个剪接点缺陷(IVS1-1G>；C，266G>；A，IVS3-1G>；A)，5个错义突变(591T>；C，627T>；A，949T>；A，1039T>；A，1512G>；C)，3个无义突变(882C>；T，1451C>；A，1569G>；T)，1个插入(756_757insA)，3个缺失(660_662deITTC，727delT，1341deIT)。这些都是新的突变。复发性肺炎、淋巴结炎和细菌性皮肤脓肿是最常见的感染类型。7名患者患有结核病(TB)。7名患者在卡介苗注射部位有长时间的疤痕或脓肿形成，我有播散性卡介苗感染。3例患者有肺曲霉菌病。4例接受了造血干细胞移植，2例死于并发症。结论：CGD患者易发生结核和卡介苗并发症。我们的观察表明，氧化爆发在宿主抵御分枝杆菌感染方面可能是重要的。由于干扰素-γ是参与分枝杆菌免疫的关键细胞因子，因此可能有更强烈的迹象表明，它适用于居住在结核病流行地区的CGD患者。
Background: Chronic granulomatous disease (CGD) is a rare disorder of phagocytic oxidative bursts leading to recurrent pyogenic infections. Affected individuals are most prone to infections caused by staphylococei, Salmonella, Candida, and Aspergillus, but previously we observed a high incidence of Mycobacterium tuberculosis infection in Chinese children with CGD.Objective: To determine the spectrum of infections in patients with X-linked CGD, with an emphasis on mycobacterial infections, and to review all CYB13 gene mutations identified in our center.Results: From 1988 to 2005, 17 Chinese male children were diagnosed to have X-linked CGD. Fifteen mutations were identified, including 3 splice site defects (IVS1-1G > C, 266G > A, IVS3-1G > A), 5 missense mutations (591T > C, 627T>A, 949T > A, 1039T > A, 1512G > C), 3 nonsense mutations (882C > T, 1451C > A, 1569G > T), 1 insertion (756_757insA), and 3 deletions (660_662deITTC, 727delT, 1341deIT). Fight of these were novel mutations. Recurrent pneumonia, lymphadenitis, and bacterial skin abscess were the commonest types of infection. Seven patients had tuberculosis (TB). Seven patients had prolonged scarring or abscess formation at the Calmette-Guerin bacillus (BCG) injection site, and I had disseminated BCG infection. Three patients had pulmonary aspergillosis. Four patients underwent hemopoietic stem cell transplantation, but 2 died of complications.Conclusions: Patients with CGD are susceptible to TB and BCG complications. Our observation suggests that oxidative burst is probably important in host defense against mycobacterial infections. Because interferon-gamma is the key cytokine involved in mycobacterial immunity, there may be a stronger indication for its use in CGD patients living in areas endemic for TB.