Clinical utility of CCL15 as a prognostic biomarker for hypersensitivity pneumonitis

Background: Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens, and the prognosis of CHP patients is poor with the absence of established diagnosing criteria and effective therapeutic agent. Recently, we have founded that C-C motif chemokine ligand 15 (CCL15) mRNA highly expressed in CHP lung. Method: To investigate the usefulness of CCL15 as a clinical biomarker for CHP, CCL15 protein expression was investigated in lung tissue, serum and bronchoalveolar lavage fluid (BALF). Results: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 μg/ml) were significantly higher than those in idiopathic pulmonary fibrosis patients (19.7 ± 1.3 μg/ml, p = 0.01) and in healthy subjects (19.5 ± 1.7 μg/ml, p = 0.003). When BALF CCL15 level was divided by BALF albumin level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (β = -0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (β = -0.41, p = 0.0048), and BALF lymphocyte count (β = -0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR = 1.1, 95% C.I. 1.03–1.18, p = 0.004). Conclusion: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP.