Chitinase activation in patients with fungus-associated cystic fibrosis lung disease

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• 作者：Andreas Hector ; MD^a ; ^&lowast ; ; Sanjay H. Chotirmall ; MD ; PhD^b ; ^&lowast ; ; Gillian M. Lavelle ; PhD^c ; Bojana Mirković ; PhD^c ; Deirdre Horan ; MD^c ; Laura Eichler ; MD^a ; Markus Mezger ; MD ; PhD^a ; Anurag Singh ; PhD^a ; Anjai Ralhan ; PhD^a ; Sina Berenbrinker ; MD^a ; Ines Mack ; MD^d ; Regina Ensenauer ; MD^e ; Joachim Riethmü ; ller ; MD^a ; Ute Graepler-Mainka ; MD^a ; Michelle A. Murray ; MD^c ; Matthias Griese ; MD^f ; N. Gerry McElvaney ; MD^c ; ^&lowast ; ; Dominik Hartl ; MD^a ; ^&lowast ; ; ^{dominik.hartl@med.uni-tuebingen.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cystic fibrosis ; lung disease ; chitinases ; chitotriosidase ; fungi ; Candida species ; neutrophils ; proteases
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：138
• 期：4
• 页码：1183-1189.e4
• 全文大小：617 K

文摘

Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)–associated lung disease remains unclear.

Objective

The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF.

Methods

Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed.

Results

Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF.

Conclusion

Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease.