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.

Abstract

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.