Enlarged, activated alveolar macrophages as quantitative surrogates of disease activity in pulmonary sarcoidosis

TL;DR

This study shows that enlarged and activated alveolar macrophages in the lungs correlate with disease activity in sarcoidosis, offering a potential new way to monitor the condition.

Contribution

The study introduces alveolar macrophage enlargement and activation as quantitative biomarkers for sarcoidosis disease activity.

Findings

Alveolar macrophages in sarcoidosis patients were 31% larger than in healthy controls.

Activation features like vacuolation and rosette formation correlated with serum ACE and sIL-2R levels.

Quantitative macrophage morphology could help assess and monitor sarcoidosis progression.

Abstract

In pulmonary sarcoidosis, alveolar macrophages (AMs) undergo epithelioid transformation, but their quantitative morphologic characteristics and association with systemic disease markers remain incompletely defined.

Do enlargement and activation features of AMs in bronchoalveolar lavage (BAL) samples correlate with systemic markers of sarcoidosis activity (ACE and sIL-2R)?

BAL cells from 16 biopsy-confirmed sarcoidosis cases and 4 healthy controls were cytocentrifuged, Diff-Quik®–stained, and analyzed using a digital planimetric microscope. Cell area (CA) of 50 randomly selected AMs per subject (total = 1,000) was quantified and categorized as small, medium, large, or extra-large based on control mean ± SD cutoffs. Nonparametric tests and principal component analysis (PCA) were applied to examine associations among CA, morphological features, serum ACE, and sIL-2R.

The mean CA was 31% greater in sarcoidosis than in controls (368.2 ± 169.3 μm2 vs. 281.4 ± 90.9 μm2; p < 0.001), with higher proportions of large/extra-large AMs (41% vs. 14%; p < 0.001). Vacuolation, rosette formation, and membrane ruffling were hallmarks of AM activation, correlating strongly with serum ACE and sIL-2R but not with the BALF CD4/CD8 ratio.

AM enlargement and activation features are quantitative, reproducible surrogates of disease activity in pulmonary sarcoidosis. Clinical implications: Quantitative assessment of alveolar macrophage morphology may aid in assessment and monitoring of sarcoidosis activity and treatment response.

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