Chemokine receptor CXCR4 based positron emission tomography imaging in systemic sclerosis-related interstitial lung disease.

OBJECTIVE

To assess chemokine receptor CXCR4 expression in lung parenchyma and on peripheral immune cells in systemic sclerosis-related interstitial lung disease (SSc-ILD) patients.

METHODS

SSc-ILD patients underwent 68Ga- CPCR4 Trifluoroacetate positron emission tomography (PET) scan, SUVmean in different lung regions and architecturally abnormal areas, and receiver operating characteristic (ROC) curves were analysed. CXCR4 expression on peripheral immune cells using flow cytometer was studied and correlated with the different lung regions. In addition, subset analysis of CXCR4 expression by clinical subset (early, progressive, stable), ILD pattern and anti-Scl-70 positivity were done.

RESULTS

On PET, SSc-ILD patients showed higher median SUVmean uptake of CXCR4 in the whole lung (0.56; P < 0.0001), different lung regions and architecturally abnormal areas than controls. The highest area under curve (AUC) was observed in dorsobasal regions (AUC-0.91; P < 0.0001) and reticular with architecturally distorted areas (AUC-0.95; P < 0.0001). The progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; P < 0.0001) and stable (0.45; P < 0.0001) subsets, and AUC than early and stable subsets. Usual interstitial pneumonia pattern ILD showed higher CXCR4 uptake compared with non-specific interstitial pneumonia (P = 0.0032). Additionally, a trend for higher uptake was noted in anti-Scl70 positive patients as compared with anti-Scl70 negative ones. SSc-ILD patients had higher CD4+CXCR4+T cells (P = 0.0003) and CD8+CXCR4+T cells (P = 0.0013) and showed moderate to strong association on correlation with the lung parenchymal regions.

CONCLUSION

In SSc-ILD, CXCR4 expression is upregulated in both lung parenchyma and peripheral T cells, significantly in progressive and UIP subsets. CXCR4 expression is a potential tool for activity assessment and prognostication.