Human cystatin C : A new biomarker of idiopathic pulmonary fibrosis?

Purpose Human idiopathic pulmonary fibrosis ( IPF ) is a progressive interstitial lung disorder with a poor prognosis. The identification of a new and specific biomarker in bronchoalveolar lavage fluids ( BALF s) may assist in the diagnosis of the disease. Experimental design Characterization of cysteine C ats and their endogenous inhibitor, cystatin C , was conducted by immunochemical analysis and measurement of endopeptidase activity of control ( n = 11) and IPF ( n = 25) BALF s (normalized conditions, 20 μg protein/assay). Results Cathepsin ( C at) B was detected as proform and mature enzyme for both control and IPF samples, while C ats K , L , and S were found as zymogens with a strengthened staining in IPF BALF s. The overall endopeptidase activity related mainly to C at B and did not vary significantly between control and IPF samples. Conversely a significant increase of immunoreactive cystatin C was measured in BALF s for each of three IPF grades. Conclusions and clinical relevance An excessive deposition of extracellular matrix proteins is the hallmark of fibrotic disorders. C ats are potent collagenases and might be essential for lung homeostasis. Taken together, increase of cystatin C in IPF BALF s may reflect abnormal regulation of proteolytic activity of C ats in lung, which in turn can promote the development of fibrosis.