M2 巨噬细胞、Th2 细胞和 B 细胞与显微镜下多血管炎并发间质性肺病的发病机制的关系。

Association of M2 Macrophages, Th2, and B Cells With Pathomechanism in Microscopic Polyangiitis Complicated by Interstitial Lung Disease.

机构信息

S. 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.

H. Kuwabara, MD, PhD, Y. Hirose, MD, PhD, Department of Pathology, Osaka Medical and Pharmaceutical University, Takatsuki.

出版信息

J Rheumatol. 2022 Aug;49(8):913-921. doi: 10.3899/jrheum.220123. Epub 2022 May 2.

DOI:10.3899/jrheum.220123

PMID:35501146

Abstract

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.

摘要

目的

通过血清生物标志物谱和肺组织病理学研究，探讨显微镜下多血管炎（MPA）并发间质性肺病（ILD）的发病机制。

方法

检测 MPA-ILD 患者（n=32）、无 ILD 的 MPA 患者（n=17）和健康对照者（n=10）的血清生物标志物。根据生物标志物谱，进行主成分分析（PCA）和聚类分析，将 MPA-ILD 患者分为亚组。评估每个亚组的临床特征和预后。对 2 例肺活检标本进行 H&E 染色和免疫组化染色。

结果

与无 ILD 的 MPA 患者相比，MPA-ILD 患者的 T 细胞和巨噬细胞极化向 Th2 细胞和 M2 巨噬细胞倾斜。PCA 可将 19 种生物标志物谱分为 3 组：（1）B 细胞和中性粒细胞相关细胞因子、血管生成相关因子、细胞外基质产生因子；（2）Th1 驱动细胞因子、M1 巨噬细胞驱动细胞因子和 Th2 驱动细胞因子；（3）M2 巨噬细胞诱导和驱动的细胞因子。聚类分析将 MPA-ILD 患者分为临床纤维增生为主型（CFD）和临床炎症为主型（CID）。值得注意的是，CFD 组的严重感染发生率明显高于 CID 组。免疫组化染色显示，MPA-ILD 患者肺间质中 B 细胞和 Th2 细胞中 CXC 基序趋化因子配体 13 染色强烈。