Increased serum YKL-40 in patients with pulmonary sarcoidosis--a potential marker of disease activity?

BACKGROUND YKL-40, a growth factor for fibroblasts and vascular endothelial cells, is secreted by macrophages and neutrophils. Elevated serum YKL-40 is found in patients with diseases characterized by inflammation, tissue remodelling and ongoing fibrosis. The aim was to evaluate whether macrophages and giant cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity. METHODS Serum YKL-40 was determined by radioimmunoassay in 27 patients with a histological diagnosis of pulmonal sarcoidosis. Immunohistochemical staining for YKL-40 antigen was performed in five biopsies with pulmonary sarcoid lesions. Serum YKL-40 was likewise measured in 173 healthy age-matched control subjects. RESULTS Mononuclear cells/macrophages and giant cells in pulmonary sarcoid granulomas expressed YKL-40 protein. Serum YKL-40 was higher in patients with pulmonary sarcoidosis compared to controls (P<0.001) and 63% had elevated serum YKL-40. There was a positive correlation between serum YKL-40 and serum angiotensin converting enzyme (rho=0.55, P=0.0053). Patients with serum YKL-40>median value in the patient group had lower carbon monoxide diffusion capacity corrected for alveolar volume (DLCO/VA) than patients with serum YKL-40 the median value (P=0.015). CONCLUSIONS Serum YKL-40 may be a novel biomarker of sarcoid disease activity and ongoing fibrosis in patients with pulmonary sarcoidosis.