Biological correlates of radiological features of systemic sclerosis interstitial lung disease.

BACKGROUND AND OBJECTIVES

The extent and pattern of radiological features ( fibrosis and ground glass) can influence treatment approaches for systemic sclerosis-related interstitial lung disease (SSc-ILD). However, the pathobiology underlying these radiological features is poorly understood and warrants further investigation.

METHODS

68 proteins were measured in bronchoalveolar lavage (BAL) fluid from 103 SSc-ILD participants in Scleroderma Lung Study I. Quantitative image analysis calculated the extent of fibrosis (QLF) and ground-glass opacity (QGG) from concurrent high-resolution computed tomography (HRCT) scans. The relationship between BAL proteins and quantitative HRCT scores was assessed by univariate and multivariate analyses.

RESULTS

QLF scores correlated weakly with the extent of QGG, suggesting two distinct processes. In a univariate analysis, 25 proteins from several biological pathways correlated with QLF scores, including profibrotic factors, tissue remodelling proteins, proteins involved in monocyte/macrophage migration and activation, and proteins linked to inflammation and immune regulation. In contrast, QGG scores correlated with only six proteins, of which four were unique and related to granulocyte activation, mobilisation of bone marrow mesenchymal stem cells and activation of T-cells, B-cells, macrophages and eosinophils. In the multivariate models, interleukin-4, CCL7, receptor activator of nuclear factor-κB and tumour necrosis factor-α were independently associated with QLF, whereas interferon-γ was independently associated with QGG.

INTERPRETATION

QLF and QGG represent distinct radiological features of SSc-ILD, a conclusion reinforced by the presence of different biological pathways present within BAL fluid that associate with each. The identified proteins and related biological pathways may represent important therapeutic targets.