{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:29:10Z","timestamp":1790710150571,"version":"4.1.0"},"reference-count":39,"publisher":"The Journal of Rheumatology","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To address the pathomechanism of microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using serum biomarker profile and pulmonary histopathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum biomarkers from patients with MPA-ILD (n = 32), MPA without ILD (n = 17), and healthy controls (n = 10) were examined. Based on the biomarker profiles, principal component analysis (PCA) and cluster analysis were performed to classify patients with MPA-ILD into subgroups. Clinical characteristics and prognosis were assessed for each subgroup. Two lung biopsies were examined following H&amp;E staining and immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>T cell and macrophage polarization was skewed toward the T helper (Th) 2 cells and M2 macrophages in the MPA-ILD group relative to that in MPA without ILD group. The PCA allowed classification of the 19 biomarker profiles into 3 groups: (1) B cell\u2013 and neutrophil-related cytokines, vascular angiogenesis-related factors, extracellular matrix-producing factors; (2) Th1-driven cytokines, M1 macrophage-driven cytokines, and Th2-driven cytokines; and (3) M2 macrophage-induced and driven cytokines. The cluster analysis stratified the patients with MPA-ILD into clinically fibrotic-dominant (CFD) and clinically inflammatory-dominant (CID) groups. Notably, severe infections were significantly higher in the CFD group than in the CID group. Immunohistochemical staining demonstrated intense CXC motif chemokine ligand 13 staining in B cells and Th2 cells in the interstitium of the lungs of patients with MPA-ILD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>The activation of M2 macrophages, Th2 cells, and B cells plays a key role in the pathomechanism of MPA-ILD. Classification of MPA-ILD based on serum biomarker profile would be useful in predicting the disease activity and the complications of severe infection in MPA-ILD.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.220123","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T18:20:14Z","timestamp":1651515614000},"page":"913-921","source":"Crossref","is-referenced-by-count":11,"title":["Association of M2 Macrophages, Th2, and B Cells With Pathomechanism in Microscopic Polyangiitis Complicated by Interstitial Lung 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