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

D. Reghellin, V. Poletti, S. Tomassetti, A. Dubini, A. Cavazza, G. Rossi, M. Lestani, S. Pedron, I. Daniele, L. Montagna, B. Murer, Marco Chilosi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalSarcoidosis Vasculitis and Diffuse Lung Diseases
Volume27
Issue number1
Publication statusPublished - Jul 2010

Fingerprint

Cathepsin K
Extrinsic Allergic Alveolitis
Interstitial Lung Diseases
Granuloma
Berylliosis
Epithelioid Cells
Granulomatosis with Polyangiitis
Bronchiolitis
Alveolar Macrophages
Sarcoidosis
Tuberculosis
Macrophages
Cryptogenic Organizing Pneumonia
Giant Cell Granuloma
Idiopathic Pulmonary Fibrosis
Langerhans Cell Histiocytosis
Cysteine Proteases
Osteoclasts
Giant Cells
Fibrosis

Keywords

  • Cathepsin-K
  • Granulomas
  • Hypersensitivity pneumonitis
  • Interstitial lung diseases

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Immunology and Allergy
  • Internal Medicine

Cite this

Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis. / Reghellin, D.; Poletti, V.; Tomassetti, S.; Dubini, A.; Cavazza, A.; Rossi, G.; Lestani, M.; Pedron, S.; Daniele, I.; Montagna, L.; Murer, B.; Chilosi, Marco.

In: Sarcoidosis Vasculitis and Diffuse Lung Diseases, Vol. 27, No. 1, 07.2010, p. 57-63.

Research output: Contribution to journalArticle

Reghellin, D, Poletti, V, Tomassetti, S, Dubini, A, Cavazza, A, Rossi, G, Lestani, M, Pedron, S, Daniele, I, Montagna, L, Murer, B & Chilosi, M 2010, 'Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis', Sarcoidosis Vasculitis and Diffuse Lung Diseases, vol. 27, no. 1, pp. 57-63.
Reghellin, D. ; Poletti, V. ; Tomassetti, S. ; Dubini, A. ; Cavazza, A. ; Rossi, G. ; Lestani, M. ; Pedron, S. ; Daniele, I. ; Montagna, L. ; Murer, B. ; Chilosi, Marco. / Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis. In: Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2010 ; Vol. 27, No. 1. pp. 57-63.
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AU - Reghellin, D.

AU - Poletti, V.

AU - Tomassetti, S.

AU - Dubini, A.

AU - Cavazza, A.

AU - Rossi, G.

AU - Lestani, M.

AU - Pedron, S.

AU - Daniele, I.

AU - Montagna, L.

AU - Murer, B.

AU - Chilosi, Marco

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