Association of M2 macrophages, Th2, and B cells with pathomechanism in microscopic polyangiitis complicated by interstitial lung disease

Objective To address the pathomechanism of microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using serum biomarker profile and pulmonary histopathology.

Methods 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 hematoxylineosin staining and immunostaining.

Results T-cell and macrophage polarization was skewed toward the T helper (Th) 2 cells and M2 macrophages in MPA-ILD group relative to that in MPA without ILD group. The PCA allowed classification of the 19 biomarker profiles into three groups: (1) B cell- and neutrophil-related cytokines, vascular angiogenesis-related factors, extracellular matrix-producing factors, (2) Th1-driven cytokines, M1 macrophagedriven 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 CXCL13 staining in B cells and Th2 cells in the interstitium of MPA-ILD lungs.

Conclusion 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 complication of severe infection in MPA-ILD.