Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis

• Published in: Sarcoidosis, vasculitis, and diffuse lung diseases Vol. 27; no. 1; pp. 57 - 63
• Main Authors: Reghellin, D, Poletti, V, Tomassett, S, Dubini, A, Cavazza, A, Rossi, G, Lestani, M, Pedron, S, Daniele, I, Montagna, L, Murer, B, Chilos, M
• Format: Journal Article
• Language: English
• Published: Italy 01-07-2010
• Subjects: Alveolitis, Extrinsic Allergic - enzymology; Alveolitis, Extrinsic Allergic - pathology; Biomarkers - analysis; Case-Control Studies; Cathepsin K - analysis; Granuloma - enzymology; Granuloma - pathology; Humans; Immunohistochemistry; Lung - enzymology; Lung - pathology; Lung Diseases, Interstitial - enzymology; Lung Diseases, Interstitial - pathology; Predictive Value of Tests; Sensitivity and Specificity
• ISSN: 1124-0490

Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that occurs upon exposure to a variety of inhaled organic antigens. The presence of small non-caseating granulomas and isolated giant cells is not specific, but is considered a relevant histological feature for HP. The detection of granulomas is widely considered as easy on standard histological stains, but microgranuloma detection can be difficult and/or time consuming, especially in chronic HP cases. Cathepsin K (Cath-K) is a potent cysteine protease expressed at high levels in activated macrophages (osteoclasts, and epithelioid cells in granulomas), but is not expressed in resident macrophages thus representing a promising marker to rapidly detect and quantitatively evaluate microgranulomas in interstitial lung diseases. We analyzed the expression of Cath-K by immunohistochemistry in 22 subacute and chronic HP cases, using semi-quantitative scores. Control samples included normal lung tissue, and a variety of interstitial lung diseases: 3 Wegener's granulomatosis, 3 sarcoidosis, 3 tuberculosis, 1 berylliosis, 20 idiopathic pulmonary fibrosis (IPF), 2 Langerhans' cell histiocytosis, 5 nonspecific-interstitial pneumonia (NSIP), 5 cryptogenic organising-pneumonia (COP), 2 Airway-Centered Interstitial Fibrosis (ACIF), 5 desquamative interstitial pneumonia (DIP), 3 respiratory bronchiolitis interstitial lung disease (RB-ILD). Intense expression of Cath-K was demonstrated in epithelioid and giant cells in all cases containing granulomas (HP, sarcoidosis, Wegener's granulomatosis, berylliosis, tuberculosis). Among HP cases 19/22 (86.3%) contained granulomas that could be semiquantitatively evaluated. In all HP and control cases alveolar macrophages did not express Cath-K, including cases characterised by large collections of alveolar macrophages such as DIP and RB-ILD.
Cath-K represents a sensitive and specific marker to detect and quantitate granulomatous reactions in interstitial lung diseases, and is particularly useful in chronic HP cases.