Indoxyl sulfate (IS) mediates pro-inflammatory responses in severe pneumonia in patients with rheumatoid arthritis associated interstitial lung disease

被引：0
作者：
Zhan, Minghua [1 ,2 ]
Li, Ziyao [3 ,4 ,5 ,6 ,7 ,8 ,9 ]
Chen, Jianing [10 ]
Zhao, Yanling [10 ]
Bai, Zhou [1 ]
Lu, Binghuai [3 ,4 ,5 ,6 ,7 ,8 ,9 ]
Chen, Hongbin [11 ]
Liu, Yudong [1 ,10 ]
机构：
[1] Chinese Acad Med Sci, Beijing Hosp, Inst Geriatr Med, Natl Ctr Gerontol,Natl Ctr Clin Labs, Beijing, Peoples R China
[2] Hebei North Univ, Affiliated Hosp 1, Dept Clin Lab, Zhangjiakou, Hebei, Peoples R China
[3] Chinese Acad Med Sci, China Japan Friendship Hosp,Inst Resp Med, Natl Ctr Resp Med,Natl Clin Res Ctr Resp Dis, Dept Pulm & Crit Care Med,Ctr Resp Med, Beijing, Peoples R China
[4] Changping Lab, Beijing, Peoples R China
[5] Dept Pulm & Crit Care Med, Lab Clin Microbiol & Infect Dis, Ctr Resp Med,China Japan Friendship Hosp, Natl Clin Res Ctr Resp Dis,Natl Ctr Resp Med, Beijing, Peoples R China
[6] China Japan Friendship Hosp, Natl Ctr Resp Med, Beijing, Peoples R China
[7] China Japan Friendship Hosp, Natl Clin Res Ctr Resp Dis, Beijing, Peoples R China
[8] Chinese Acad Med Sci, Inst Resp Med, Beijing, Peoples R China
[9] China Japan Friendship Hosp, Ctr Resp Med, Dept Pulm & Crit Care Med, Beijing, Peoples R China
[10] Chinese Acad Med Sci & Peking Union Med Coll, Clin Immunol Ctr, Inst Geriatr Med, Dept Rheumatol,Beijing Hosp,Natl Ctr Gerontol, Beijing, Peoples R China
[11] Peking Univ, Peoples Hosp, Dept Clin Lab, Beijing, Peoples R China
来源：
CLINICAL IMMUNOLOGY | 2025年 / 272卷
基金：
中国国家自然科学基金;
关键词：
Rheumatoid arthritis-associated interstitial lung disease; COVID-19; Pneumonia; Lower respiratory tract microbiome; Metabolomics; POPULATION; CANCER;
D O I：
10.1016/j.clim.2025.110430
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Object: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have a high risk of serious infection, in particular severe pneumonia. This study aimed to investigate the transcriptional landscape, lower respiratory tract (LRT) microbiome and metabolomic profiles in the lung of RA-ILD patients with pneumonia. Method: A total of 10 RA-ILD with pneumonia were enrolled in this study. In addition, 11 patients with COVID19-associated pneumonia and 6 patients with non-autoimmune and non-COVID-19-related ILD with pneumonia were included as controls. Bronchoalveolar lavage fluid (BALF) was collected and prepared for metagenomic next-generation sequencing (mNGS), non-targeted metabolomics and bulk RNA-seq. Result: Neutrophil-related genes were shared in the BALF cells of RA-ILD patients with pneumonia and patients with COVID-19-associated pneumonia. Carnobacterium, Wujia, Intestinimonas, Apibacter, Anaerotignum and Parvimonas were enriched in the LRT microbiome of RA-ILD, while Wujia, Apibacter, Pseudocitrobacter, and Thermobacillus were enriched in the LRT microbiome of COVID-19. Metabolomics analysis of BALF revealed significant elevation of indoxyl sulfate (IS) in the BALF of RA-ILD patients in comparison to COVID-19. Mechanistically, IS exerts an pro-inflammatory effect on macrophages and bronchial epithelial cells for pro- inflammatory cytokine production and potentiated neutrophils for neutrophil extracellular traps (NETs) formation. Conclusions: Our results demonstrated a significant differences in the LRT microbiome and BALF metabolites between RA-ILD and COVID-19 patients with pneumonia, although they displayed similar local immune responses against lung infection. Alterations of LRT microbiome and related metabolites may be implicated in the pathogenesis of pneumonia in RA-ILD.
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页数：10
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