title: Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Verona, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Reghellin
authors.forename: V
authors.initials: V
authors.lastname: Poletti
authors.forename: S
authors.initials: S
authors.lastname: Tomassett
authors.forename: A
authors.initials: A
authors.lastname: Dubini
authors.forename: A
authors.initials: A
authors.lastname: Cavazza
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Lestani
authors.forename: S
authors.initials: S
authors.lastname: Pedron
authors.forename: I
authors.initials: I
authors.lastname: Daniele
authors.forename: L
authors.initials: L
authors.lastname: Montagna
authors.forename: B
authors.initials: B
authors.lastname: Murer
authors.forename: M
authors.initials: M
authors.lastname: Chilos
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D056657:Cathepsin K / Q000032:analysis*; D006099:Granuloma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C534130:CTSK protein, human; D056657:Cathepsin K