Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan,
J Clin Immunol. 2014 Nov;34(8):933-40. doi: 10.1007/s10875-014-0089-1. Epub 2014 Sep 4.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. CGD patients also suffer from immune regulatory disorders, such as CGD-associated bowel inflammation with granuloma, which could be caused by excessive inflammation without demonstrable infection.
We investigated the clinical manifestation of interstitial lung disease (ILD) resulting from excessive inflammation in X-linked CGD patients.
Pulmonary CT images and testing of serum KL-6 levels were performed to assess ILD in the patients. For this study, patients with pulmonary lesions due to demonstrable infections were excluded from among ILD patients.
Among 33 CGD patients, four developed ILD; they had increased reticulo-nodular opacities on CT images and elevated serum KL-6 levels. Histopathological examinations revealed multiple homogeneous microgranulomas in the lesions of inflammatory cell infiltration. Mononuclear cells obtained from their pulmonary lesions produced higher amounts of inflammatory cytokines than the peripheral blood mononuclear cells of CGD patients, suggesting that the only infiltrating cells in the pulmonary lesions were activated and produced large amounts of inflammatory cytokines in ILD patients. Interestingly, an anti-inflammatory drug, such as a corticosteroid or thalidomide, but not anti-bacterial or anti-fungal drugs, improved CT image findings and reduced their KL-6 levels.
CGD patients' daily exposures to inhaled antigens may induce excessive reactions with the production of inflammatory cytokines leading to the development of ILD with multiple microgranulomas, which could be due to an inadequate production of reactive oxygen species in CGD.
慢性肉芽肿病（CGD）是一种原发性免疫缺陷病，其特征是易发生细菌和真菌感染。CGD 患者还患有免疫调节紊乱，如 CGD 相关的肉芽肿性肠炎，这可能是由于炎症过度而无明显感染引起的。
我们研究了 X 连锁 CGD 患者过度炎症引起的间质性肺病（ILD）的临床表现。
对患者进行肺部 CT 图像检查和血清 KL-6 水平检测，以评估 ILD。在这项研究中，ILD 患者排除了因明显感染而导致肺部病变的患者。
在 33 名 CGD 患者中，有 4 名患者发生了 ILD；他们的 CT 图像上有网状结节状混浊增加，血清 KL-6 水平升高。组织病理学检查显示，炎症细胞浸润的病变中有多个均匀的微肉芽肿。从他们的肺部病变中获得的单核细胞比 CGD 患者的外周血单核细胞产生更多的炎症细胞因子，这表明在 ILD 患者的肺部病变中只有浸润的细胞被激活并产生大量的炎症细胞因子。有趣的是，一种抗炎药，如皮质类固醇或沙利度胺，但不是抗细菌或抗真菌药物，改善了 CT 图像的发现，并降低了他们的 KL-6 水平。
CGD 患者每天接触吸入性抗原可能会引起过度反应，产生炎症细胞因子，导致 ILD 伴多发微肉芽肿形成，这可能是由于 CGD 中活性氧物质产生不足所致。
