LAUSR

Simple Summary Krebs von den Lungen-6 (KL-6) is a mucin involved in several cellular processes, and its expression increases following injured or regenerating type II pneumocyte. KL-6 was suggested to identify patients affected by fibrotic interstitial lung diseases (ILD) associated with rheumatologic disorders. This is the first study that has assessed whether serum KL-6 can distinguish ANCA-associated vasculitis (AAV) patients with ILD from those without ILD, and whether this biomarker and its changes over time are correlated with disease activity, vasculitic damage, and response to treatment. Thirteen AAV patients were enrolled, four of them with ILD. Higher serum KL-6 was found in AAV-ILD patients in comparison with those without ILD. The best KL-6 cutoff values of 368 U/mL and 301 U/mL at baseline and during follow-up, respectively, were suggested to distinguish the two groups. A direct correlation was found between serum KL-6 and disease activity. Our multicenter study demonstrated KL-6 as a reliable, non-invasive, and easy-to-perform marker of ILD in AAV patients, being helpful for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile. Abstract Background: ANCA-associated vasculitis (AAV) are small vessel vasculitis distinguished between microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). The former may have interstitial lung disease (ILD) associated with high morbidity and mortality. Here, Krebs von den Lungen-6 (KL-6), a marker of fibrotic ILD, was assessed for distinguishing AAV patients with ILD from those without ILD, and whether its changes over time are correlated with disease activity. Materials and Methods: Thirteen AAV patients (eight females, mean age 61 ± 14.8 years) were enrolled: six MPA and six GPA. Serum samples were assayed for KL-6 concentrations (Fujirebio Europe, Belgium). To investigate potential binary classifiers for diagnosis of AAV-ILD, we constructed a regression decision tree model. Results: Higher serum KL-6 were in AAV-ILD compared with those without ILD (972.8 ± 398.5 vs 305.4 ± 93.9, p = 0.0040). Area under the receiver operating characteristics curve showed 100% of the diagnostic performance of KL-6 for identifying the ILD involvement (accuracy 91.7%) and the best cutoff value of 368 U/mL (sensitivity 100% and specificity 87.5%). The decision tree model showed a 33% improvement in class purity using a cut-off value of 513 U/mL to distinguish AAV patients with and without ILD. Stratifying AAV patients as MPA and GPA with and without ILD considering T0 and T1 KL-6, the model obtained an improvement of 40% for classifying GPA non-ILD with a T0 serum KL-6 cut-off value of 513 U/mL and a T1 KL-6 cut-off of 301 U/mL. A direct correlation was found between serum T0 KL-6 and T0 BVAS (r = 0.578, p = 0.044). Conclusion: Our multicenter study demonstrated KL-6 as a reliable, non-invasive, and easy-to-perform marker of ILD in AAV patients and its helpfulness for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile.