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Association of M2 Macrophages, Th2, and B Cells With Pathomechanism in Microscopic Polyangiitis Complicated by
Shogo Matsuda1, Takuya Kotani1, Hiroko Kuwabara2
1S. Matsuda, MD, PhD, T. Kotani, MD, PhD, T Suzuka, MD, PhD, T. Kiboshi, MD, Y Wada, MD, PhD, T Ishida, MD, PhD, H. Shiba, MD, K. Hata, MD, T. Shoda, MD, T Takeuchi, MD, PhD, Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University, Takatsuki.
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 H&E staining and immunostaining.
Results:
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- 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.
Conclusion:
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.
Insights
Microscopic polyangiitis with interstitial lung disease (MPA-ILD) involves M2 macrophages, Th2 cells, and B cells. Serum biomarkers can predict MPA-ILD activity and infection risk.
Area of Science:
- Immunology
- Pulmonology
- Rheumatology
Background:
- Microscopic polyangiitis (MPA) is a systemic vasculitis that can affect the lungs.
- Interstitial lung disease (ILD) is a serious complication of MPA, impacting patient prognosis.
- Understanding the pathomechanism of MPA-ILD is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the pathomechanism of MPA complicated by ILD (MPA-ILD).
- To analyze serum biomarker profiles and pulmonary histopathology in MPA-ILD patients.
- To classify MPA-ILD patients into subgroups based on biomarker profiles for prognostic assessment.
Main Methods:
- Serum biomarkers were analyzed from patients with MPA-ILD, MPA without ILD, and healthy controls.
- Principal component analysis (PCA) and cluster analysis were used to classify biomarker profiles.
- Lung biopsies were examined using H&E staining and immunohistochemistry.
Main Results:
- MPA-ILD showed a skew towards T helper (Th) 2 cells and M2 macrophages compared to MPA without ILD.
- PCA identified three distinct biomarker profile groups.
- Cluster analysis stratified MPA-ILD patients into clinically fibrotic-dominant (CFD) and inflammatory-dominant (CID) groups, with higher severe infection rates in CFD.
- Immunohistochemistry revealed intense CXC motif chemokine ligand 13 staining in lung interstitium.
Conclusions:
- M2 macrophage, Th2 cell, and B cell activation are key in MPA-ILD pathogenesis.
- Serum biomarker profiling aids in predicting MPA-ILD disease activity.
- Biomarker-based classification can help identify patients at risk for severe infections.
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