Omaru Naoya, Watanabe Tomohiro, Hara Akane, Kurimoto Masayuki, Masuta Yasuhiro, Otsuka Yasuo, Masaki Sho, Minaga Kosuke, Kamata Ken, Honjo Hajime, Arai Yasuyuki, Yamashita Kouhei, Kudo Masatoshi
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan;
In Vivo. 2025 Jul-Aug;39(4):1902-1911. doi: 10.21873/invivo.13989.
BACKGROUND/AIM: Chronic granulomatous disease (CGD) is a hereditary immune deficiency caused by mutations in nicotinamide adenine dinucleotide phosphate oxidase subunits. X-linked CGD caused by mutations in gp91 is characterized by recurrent bacterial and fungal infections and by an increased incidence of autoimmunity and inflammatory bowel disease (IBD). The concurrent occurrence of microbial infection, autoimmunity, and IBD suggests the presence of complicated profiles of cytokines in patients with CGD. However, the pro-inflammatory and anti-inflammatory cytokine responses to microbe-associated molecular patterns (MAMPs) are poorly defined in patients with CGD.
We evaluated the cytokine and chemokine profiles in two patients with X-linked CGD. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with various bacterial and fungal MAMPs.
Production of C-X-C motif chemokine ligand 8, interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α was enhanced by PBMCs isolated from patients with X-linked CGD as compared with those from healthy controls when stimulated with bacterial and fungal MAMPs.
A dysregulated balance between pro-inflammatory and anti-inflammatory cytokines may contribute to the manifestations of recurrent infection, autoimmunity, and IBD in patients with X-linked CGD.
背景/目的：慢性肉芽肿病（CGD）是一种由烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基突变引起的遗传性免疫缺陷病。由gp91突变导致的X连锁CGD的特征为反复发生细菌和真菌感染，以及自身免疫性疾病和炎症性肠病（IBD）的发病率增加。微生物感染、自身免疫和IBD同时出现提示CGD患者存在复杂的细胞因子谱。然而，CGD患者对微生物相关分子模式（MAMP）的促炎和抗炎细胞因子反应尚不明确。
我们评估了两名X连锁CGD患者的细胞因子和趋化因子谱。分离外周血单个核细胞（PBMC），并用各种细菌和真菌MAMP进行刺激。
与健康对照者的PBMC相比，当用细菌和真菌MAMP刺激时，X连锁CGD患者的PBMC增强了C-X-C基序趋化因子配体8、白细胞介素-6（IL-6）、IL-10和肿瘤坏死因子-α的产生。
促炎和抗炎细胞因子之间的平衡失调可能导致X连锁CGD患者反复感染、自身免疫和IBD的表现。
