Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers.

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=0.01. 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<0.001. KL-6 correlated with IgG antibody titre in those with symptoms, r=0.591, p=0.006. High KL-6, irrespective of symptom category, was associated with higher antibody (p=0.006) and lymphocyte proliferation (p=0.041), and lower CD4+ T-lymphocyte proportion (p=0.032). 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.