Interstitial Lung Disease with Multiple Microgranulomas in Chronic Granulomatous Disease.
Interstitial Lung Disease with Multiple Microgranulomas in Chronic Granulomatous Disease.
复制标题
慢性肉芽肿病中伴有多发性微肉芽肿的间质性肺病。
DOI：
10.1007/s10875-014-0089-1
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发表时间：
2014
影响因子：
9.1
通讯作者：
Onodera M
中科院分区：
文献类型：
--
作者：
Kawai T;Watanabe N;Yokoyama M;Nakazawa Y;Goto F;Uchiyama T;Higuchi M;Maekawa T;Tamura E;Nagasaka S;Hojo M;Onodera M
研究背景慢性肉芽肿病（CGD）是一种原发性免疫缺陷疾病，其特征是易受细菌和真菌感染。 CGD患者还患有免疫调节紊乱，如CGD相关的肠道炎症伴肉芽肿，这可能是由于过度炎症而无明显感染所致。目的我们调查X连锁CGD患者过度炎症导致的间质性肺疾病（ILD）的临床表现。方法采用肺部CT图像和血清KL-6水平检测。 旨在评估患者的 ILD。在本研究中，因明显感染而导致肺部病变的患者被排除在 ILD 患者之外。结果 在 33 名 CGD 患者中，4 名发展为 ILD；4 名发展为 ILD；4 名发展为 ILD。 CT 图像上网状结节性混浊增加，血清 KL-6 水平升高。组织病理学检查发现病灶内有多发均一的微肉芽肿，炎细胞浸润。从肺部病灶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性细胞因子，这表明ILD患者中肺部病灶中唯一的浸润细胞被激活并产生大量的炎性细胞因子。有趣的是，抗炎药物，如皮质类固醇或沙利度胺，但不是抗菌或抗真菌药物，可以改善 CT 图像表现并降低 KL-6 水平。结论 CGD 患者每天接触吸入抗原可能会引起过度反应，产生炎症细胞因子，导致 ILD 的发展并伴有多发性微肉芽肿，这可能会导致 ILD 的发生。 这是由于 CGD 中活性氧生成不足所致。
BackgroundChronic 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.PurposeWe investigated the clinical manifestation of interstitial lung disease (ILD) resulting from excessive inflammation in X-linked CGD patients.MethodsPulmonary 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.ResultsAmong 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.ConclusionsCGD 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.