TY - JOUR
T1 - Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers
AU - Ji, Yuan
AU - Bourke, Stephen J.
AU - Spears, Mark
AU - Wain, Louise V.
AU - Boyd, Gavin
AU - Lynch, Phillip P.
AU - Cunningham, Matthew
AU - Boyd, Kenneth
AU - Donnelly, Iona
AU - Kohno, Nobuoki
AU - McSharry, Charles
N1 - Funding Information:
This work was funded by The British Pigeon Fanciers Medical Research Trust and Institutional funds.
Funding Information:
This study is testament to the support of pigeon fanciers who volunteered their unique insight of the symptom patterns of this form of interstitial lung disease. We thank Dr Lynch for providing pigeon antigens. L V Wain holds a GlaxoSmithKline/British Lung Foundation Chair in Respiratory Research. The research was partially supported by the NIHR Leicester Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Yuan Ji was supported by China Scholarship Council (CSC) grant number 201708060324, and University of Glasgow tuition and subsistence funds. Funding support and governance from the British Pigeon Fanciers Medical Research Trust (SCO1318) is gratefully acknowledged: Trustees Dr Philip Lynch (Chairman), Dr Gavin Boyd (Research and Medical Director), Dr Kenneth Anderson, Mr George Pollock (Treasurer), Mr Iain Orr, Mr William Frame (Pres. SNFC) and Mr Samuel Macfadzen (deceased).
Funding Information:
This work was funded by The British Pigeon Fanciers Medical Research Trust and Institutional funds. This study is testament to the support of pigeon fanciers who volunteered their unique insight of the symptom patterns of this form of interstitial lung disease. We thank Dr Lynch for providing pigeon antigens. L V Wain holds a GlaxoSmithKline/British Lung Foundation Chair in Respiratory Research. The research was partially supported by the NIHR Leicester Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Yuan Ji was supported by China Scholarship Council (CSC) grant number 201708060324, and University of Glasgow tuition and subsistence funds. Funding support and governance from the British Pigeon Fanciers Medical Research Trust (SCO1318) is gratefully acknowledged: Trustees Dr Philip Lynch (Chairman), Dr Gavin Boyd (Research and Medical Director), Dr Kenneth Anderson, Mr George Pollock (Treasurer), Mr Iain Orr, Mr William Frame (Pres. SNFC) and Mr Samuel Macfadzen (deceased).
Publisher Copyright:
© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Background: Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP. Objective: To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP. Methods: Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production.Results: KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P =.01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P <.001. KL-6 correlated with IgG antibody titre in those with symptoms, r =.591, P =.006. High KL-6, irrespective of symptom category, was associated with higher antibody (P =.006) and lymphocyte proliferation (P =.041), and lower CD4+ T lymphocyte proportion (P =.032). Conclusion and Clinical Relevance: Raised KL-6 is associated with acute symptoms of early-stage HP, and its correlation with antibody may support therapeutic strategies when HP is suspected. KL-6 may act as a mechanistic biomarker of early pathogenesis by linking lung pathophysiological changes with an endotype of immune hypersensitivity.
AB - Background: Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP. Objective: To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP. Methods: Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production.Results: KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P =.01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P <.001. KL-6 correlated with IgG antibody titre in those with symptoms, r =.591, P =.006. High KL-6, irrespective of symptom category, was associated with higher antibody (P =.006) and lymphocyte proliferation (P =.041), and lower CD4+ T lymphocyte proportion (P =.032). Conclusion and Clinical Relevance: Raised KL-6 is associated with acute symptoms of early-stage HP, and its correlation with antibody may support therapeutic strategies when HP is suspected. KL-6 may act as a mechanistic biomarker of early pathogenesis by linking lung pathophysiological changes with an endotype of immune hypersensitivity.
KW - biomarkers
KW - hypersensitivity pneumonitis
KW - ILD
KW - KL-6
UR - http://www.scopus.com/inward/record.url?scp=85092156040&partnerID=8YFLogxK
U2 - 10.1111/cea.13744
DO - 10.1111/cea.13744
M3 - Article
C2 - 32966647
AN - SCOPUS:85092156040
SN - 0954-7894
VL - 50
SP - 1391
EP - 1399
JO - Clinical and Experimental Allergy
JF - Clinical and Experimental Allergy
IS - 12
ER -