Prediction of Chronic Lung Allograft Dysfunction by Monitoring Serum KL-6 Levels

Purpose Chronic lung allograft dysfunction (CLAD) is the main cause of long-term mortality in lung transplantation (LT). The main phenotypes of CLAD are bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and mixed. Biomarkers for early identification of CLAD are needed. KL-6, an antigen produced mainly by damaged type II pneumocytes, has been described as a RAS-biomarker. The aim of our study was to assess the utility of serum KL-6 levels as a CLAD biomarker. Methods This was a longitudinal study in which KL-6 levels were measured in 52 bilateral LT patients at 3, 6, 9, 12, 18 and 24 months after LT. At the same time-points, clinical features and pulmonary function were determined. CLAD diagnosis was assessed during a three years follow-up. Results Seventeen out of 52 patients developed CLAD (11 BOS and 6 patients RAS or mixed). No differences in demographics were found, but patients with RAS or mixed phenotypes had a higher incidence of positive Donor-Specific Antibodies (DSA). Also, serum KL-6 levels before CLAD diagnosis were higher in the patients who developed RAS-mixed (563 [439.7-752.8 U/ml]) compared to patients diagnosed with BOS (356.7 [265.7-492.2 U/ml]) or those without CLAD (372.8 [274.8-606.9 U/ml]) at 6 months after LT, although not statistically significant (p=0.187). However, a KL-6 cut-off of 520.4 U/ml at 6-month post-transplant was able to differentiate RAS-mixed from non- RAS-mixed patients with a sensitivity of 80% (IC95 28.36-99.49%) and specificity of 72.73% (IC95 57.21-85.04%). When analyzing serum KL-6 levels in all samples, even those obtained after CLAD diagnosis, RAS patients had higher levels which progressively increase along follow-up (see table). Conclusion Serum KL-6 could be a useful biomarker for RAS prediction. Chronic lung allograft dysfunction (CLAD) is the main cause of long-term mortality in lung transplantation (LT). The main phenotypes of CLAD are bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and mixed. Biomarkers for early identification of CLAD are needed. KL-6, an antigen produced mainly by damaged type II pneumocytes, has been described as a RAS-biomarker. The aim of our study was to assess the utility of serum KL-6 levels as a CLAD biomarker. This was a longitudinal study in which KL-6 levels were measured in 52 bilateral LT patients at 3, 6, 9, 12, 18 and 24 months after LT. At the same time-points, clinical features and pulmonary function were determined. CLAD diagnosis was assessed during a three years follow-up. Seventeen out of 52 patients developed CLAD (11 BOS and 6 patients RAS or mixed). No differences in demographics were found, but patients with RAS or mixed phenotypes had a higher incidence of positive Donor-Specific Antibodies (DSA). Also, serum KL-6 levels before CLAD diagnosis were higher in the patients who developed RAS-mixed (563 [439.7-752.8 U/ml]) compared to patients diagnosed with BOS (356.7 [265.7-492.2 U/ml]) or those without CLAD (372.8 [274.8-606.9 U/ml]) at 6 months after LT, although not statistically significant (p=0.187). However, a KL-6 cut-off of 520.4 U/ml at 6-month post-transplant was able to differentiate RAS-mixed from non- RAS-mixed patients with a sensitivity of 80% (IC95 28.36-99.49%) and specificity of 72.73% (IC95 57.21-85.04%). When analyzing serum KL-6 levels in all samples, even those obtained after CLAD diagnosis, RAS patients had higher levels which progressively increase along follow-up (see table). Serum KL-6 could be a useful biomarker for RAS prediction.