76b5e68a6ce5087e9a25c7ce6bc187b0 275158.pdf dd23ea23530f0880b9d9ec0949a988248b09d572 275158.pdf df5196da798dda920c61fc018977b60a8b5503bf679358d13be5ce935addab3c 275158.pdf Title: Association between Changes in the Patterns of Antinuclear Autoantibodies during Immune Checkpoint Inhibition Therapy and the Development of Severe Immune Related Adverse Events Subject: Immune-related adverse events (irAEs) are unpredictable autoimmune-like toxicities induced by immune checkpoint inhibitors (ICI). irAEs are a consequence of a breakdown in self-tolerance. ICIs can induce autoantibody formation, and the presence of antinuclear autoantibodies (ANAs) has been reported in patients who developed irAEs. Our goal was to compare ANA patterns by indirect immunofluorescence at different timepoints before (baseline) and after the initiation of ICI treatment and to analyze the role of ANA pattern changes as predictors of irAEs. This is a 2-year-follow-up prospective study of 152 consecutive patients with solid tumors treated with anti-PD-(L)1 blockade agents. They were included from September 2018 until March 2020 in the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). We grouped patients into three groups: ANA de novo (patients who showed new ANA patterns at any time after ICI initiation), ANA (ANA positive at baseline without changes in the ANA patterns after initiation of treatment) and non-ANA (ANA negative at baseline and after ICI initiation). We did not find any association between the appearance of ANAs and irAE rates or the number and types of irAEs. However, patients in the ANA de novo group showed higher severe irAE rates (grade 3) than the other groups. Additionally, in most of the patients with severe irAEs (83.3%), changes in ANA patterns preceded irAE onset. In conclusion, we found ANA induction during ICI therapies in 22 patients and our results suggest that the appearance of ANAs may predict the severity of the irAE. Keywords: immune-related adverse events (irAEs); anti-PD-(L)1 blocking agents; antinuclear autoantibodies (ANA); predictive biomarkers; immune checkpoint inhibitors Author: Leticia Alserawan, Geòrgia Anguera, Carlos Zamora Atenza, Jorgina Serra López, Laura Martínez-Martínez, Mariona Riudavets Melià, Ivana Sullivan, Andrés Barba Joaquin, Margarita Majem Tarruella and Silvia Vidal Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Oct 25 04:04:58 2022 CEST ModDate: Tue Oct 25 04:19:05 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1239982 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SGWBNM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ZZGSHN+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ECCKEB+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 DQTFUL+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 LFLYLN+CMSY10 Type 1 Builtin yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 46 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 74 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 86 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 90 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 94 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 98 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 114 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 118 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 122 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 126 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 148 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 152 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 156 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 160 0 CIQLLF+VnURWPalladioL Type 1 Custom yes yes no 177 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-08 02:27:58 CEST RepresentationInformation: 275158.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-07 10:39:13 CEST Size: 1239982 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 339 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Background Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Patients’ Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: IrAE Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: ANA Pattern Appearance during ICI Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Association between ANA Development and IrAEs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Sample Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Detection of Antinuclear Antibodies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: Association between Changes in the Patterns of Antinuclear Autoantibodies during Immune Checkpoint Inhibition Therapy and the Development of Severe Immune Related Adverse Events Author: Leticia Alserawan, Geòrgia Anguera, Carlos Zamora Atenza, Jorgina Serra López, Laura Martínez-Martínez, Mariona Riudavets Melià, Ivana Sullivan, Andrés Barba Joaquin, Margarita Majem Tarruella and Silvia Vidal Subject: Immune-related adverse events (irAEs) are unpredictable autoimmune-like toxicities induced by immune checkpoint inhibitors (ICI). irAEs are a consequence of a breakdown in self-tolerance. ICIs can induce autoantibody formation, and the presence of antinuclear autoantibodies (ANAs) has been reported in patients who developed irAEs. Our goal was to compare ANA patterns by indirect immunofluorescence at different timepoints before (baseline) and after the initiation of ICI treatment and to analyze the role of ANA pattern changes as predictors of irAEs. This is a 2-year-follow-up prospective study of 152 consecutive patients with solid tumors treated with anti-PD-(L)1 blockade agents. They were included from September 2018 until March 2020 in the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). We grouped patients into three groups: ANA de novo (patients who showed new ANA patterns at any time after ICI initiation), ANA (ANA positive at baseline without changes in the ANA patterns after initiation of treatment) and non-ANA (ANA negative at baseline and after ICI initiation). We did not find any association between the appearance of ANAs and irAE rates or the number and types of irAEs. However, patients in the ANA de novo group showed higher severe irAE rates (grade 3) than the other groups. Additionally, in most of the patients with severe irAEs (83.3%), changes in ANA patterns preceded irAE onset. In conclusion, we found ANA induction during ICI therapies in 22 patients and our results suggest that the appearance of ANAs may predict the severity of the irAE. 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