7d95961e25bcd8633a8598b589b81f60 277685.pdf d59a8989c9bc11da2fb5be404765430c0bb4cac1 277685.pdf 99cb19b164f26843dffcc193dddef06191d0c4a25f81ed6031b17fc602122a70 277685.pdf Title: KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach Subject: 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. Keywords: KL-6; ANCA-associated vasculitis; interstitial lung disease Author: Edoardo Conticini, Miriana d’Alessandro, Laura Bergantini, Diego Castillo, Paolo Cameli, Bruno Frediani, Luca Cantarini and Elena Bargagli Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jan 19 11:19:48 2022 CET ModDate: Wed Jan 19 11:26:16 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1608722 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ABIRAR+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 LTEDCL+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 DHQGWZ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 LGTZLE+CMSY10 Type 1 Builtin yes yes no 23 0 OPZDHV+VnURWPalladioL Type 1 Custom yes yes no 27 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 GLCFZC+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 GEAPEO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 90 0 GEAPFA+PalatinoLinotype TrueType WinAnsi yes yes no 93 0 GEAPFC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 96 0 GEAPEO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 106 0 GEAPFA+PalatinoLinotype TrueType WinAnsi yes yes no 109 0 GEAPFC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 112 0 GEAPEO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 119 0 GEAPFA+PalatinoLinotype TrueType WinAnsi yes yes no 122 0 GEAPFC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 125 0 GEBCLO+Arial,Bold CID TrueType Identity-H yes yes yes 128 0 GEBCLP+TimesNewRoman CID TrueType Identity-H yes yes yes 134 0 GEAPEO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 147 0 GEAPFA+PalatinoLinotype TrueType WinAnsi yes yes no 150 0 GEAPFC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 153 0 GEBCLO+Arial,Bold CID TrueType Identity-H yes yes yes 156 0 GEBCLP+TimesNewRoman CID TrueType Identity-H yes yes yes 162 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-18 02:34:04 CEST RepresentationInformation: 277685.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-17 14:56:00 CEST Size: 1608722 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 273 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Info: Title: KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach Author: Edoardo Conticini, Miriana d’Alessandro, Laura Bergantini, Diego Castillo, Paolo Cameli, Bruno Frediani, Luca Cantarini and Elena Bargagli Subject: 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. 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