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CCL2 produced by CD68+/CD163+ macrophages as a promising clinical biomarker of microscopic polyangiitis-interstitial
Shogo Matsuda1, Takuya Kotani1, Hiroko Kuwabara2
1Department of Internal Medicine (IV).
Objectives:
Microscopic polyangiitis (MPA) is often complicated by interstitial lung disease (ILD); however, biomarkers that can be used to diagnose and predict the progression of MPA-ILD have not been identified. In this study, we evaluated various serum biomarkers in MPA-ILD to assess their diagnostic and predictive performance.
Methods:
We enrolled 49 patients with anti-neutrophil cytoplasmic antibody (ANCA)+ MPA and 10 healthy controls, with 32 of the MPA patients also presenting ILD. The presence of ILD was assessed by high-resolution CT and evaluated by ground-glass opacity and fibrosis score. We compared 16 biomarker profiles among MPA-ILD patients, those without ILD, and healthy controls and extracted biomarkers with higher levels in MPA-ILD groups to determine correlations with disease activity and other biomarkers. Three lung biopsies were examined by haematoxylin-eosin staining and immunostaining.
Results:
Initial serum C-C motif chemokine ligand 2 (CCL2) levels were significantly higher in the MPA-ILD group than those of the MPA group, and were significantly higher in MPA-ILD patients 1 year after immunosuppressive therapy than those before treatment. Initial serum CCL2 levels positively correlated with an increased fibrosis score during the year after treatment and with initial serum platelet-derived growth factor levels. Immunohistochemical staining showed intense CCL2 signals in CD68+/CD163+ macrophages and metaplastic epithelial cells in MPA-ILD lungs.
Conclusion:
CCL2 is associated with MPA-ILD pathogenesis and suggested its potential efficacy as a useful marker for diagnosing and predicting MPA-ILD progression. Therefore, targeting CCL2 in alveolar CD68+/CD163+ macrophages might represent a therapeutic intervention in ANCA+ MPA-ILD.
Insights
Serum C-C motif chemokine ligand 2 (CCL2) is a potential biomarker for diagnosing and predicting microscopic polyangiitis with interstitial lung disease (MPA-ILD). Higher CCL2 levels correlate with fibrosis and disease progression in MPA-ILD patients.
Area of Science:
- Immunology
- Pulmonology
- Rheumatology
Background:
- Microscopic polyangiitis (MPA) frequently involves interstitial lung disease (ILD).
- Effective biomarkers for diagnosing and predicting MPA-ILD progression are lacking.
- This study investigates serum biomarkers in MPA-ILD.
Purpose of the Study:
- To evaluate serum biomarkers for diagnosing and predicting MPA-ILD.
- To identify correlations between biomarkers, disease activity, and fibrosis.
- To explore the role of C-C motif chemokine ligand 2 (CCL2) in MPA-ILD pathogenesis.
Main Methods:
- 49 anti-neutrophil cytoplasmic antibody (ANCA)+ MPA patients (32 with ILD) and 10 controls were enrolled.
- High-resolution CT assessed ILD severity (ground-glass opacity, fibrosis).
- 16 serum biomarkers were compared; lung biopsies were analyzed via immunohistochemistry.
Main Results:
- Serum C-C motif chemokine ligand 2 (CCL2) levels were significantly higher in MPA-ILD patients compared to MPA patients without ILD.
- CCL2 levels remained elevated one year post-immunosuppressive therapy.
- CCL2 positively correlated with fibrosis score and platelet-derived growth factor; intense CCL2 signals were found in lung macrophages.
Conclusions:
- CCL2 is implicated in MPA-ILD pathogenesis.
- CCL2 shows potential as a diagnostic and predictive marker for MPA-ILD.
- Targeting CCL2 in macrophages may offer a therapeutic strategy for ANCA+ MPA-ILD.
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