2e135778a72eb9825972262a8699a237 cells-14-01156.pdf ee35bee12a69df033a5548f73869221507c53e77 cells-14-01156.pdf 6708a7760e75b4a75cdec430bf3fc846ddeb8684b3efab6cd1278e9b0a485978 cells-14-01156.pdf Title: Impaired Long-Term Quantitative Cellular Response to SARS-CoV-2 Vaccine in Thiopurine-Treated IBD Patients Subject: Background: Studies investigating the long-term cellular immune response to SARS-CoV-2 mRNA vaccines in patients with inflammatory bowel disease (IBD) remain limited, particularly among those receiving immunosuppressive therapy. Methods: We prospectively evaluated humoral and cellular immune responses at short-term (4–6 weeks) and long-term (6–12 months) time points following SARS-CoV-2 mRNA vaccination in patients with IBD receiving anti-TNF agents, thiopurines, or combination therapy. We defined the short-term response as the measurement taken 4–6 weeks after the second vaccine dose and the long-term response as the measurement taken between 6 and 12 months after the first determination. A cohort of healthy controls was included for short-term comparative analysis. Results: At long-term follow-up, quantitative humoral responses were reduced in patients receiving anti-TNF monotherapy. In contrast, a reduced quantitative cellular response was found in the thiopurine (median 0.7 UI/mL, p < 0.05) and anti-TNF combo groups (median 0.4 UI/mL, p < 0.01) compared to anti-TNF monotherapy (median 2.2 UI/mL). Conclusions: There was a robust long-term humoral and cellular response to vaccination, but a diminished quantitative cellular response in patients treated with thiopurines or combo therapy compared to anti-TNF monotherapy. Keywords: SARS-CoV2 vaccine; inflammatory bowel disease; cellular response; thiopurines Author: Luis Mayorga Ayala, Claudia Herrera-deGuise, Juliana Esperalba, Xavier Martinez-Gomez, Elena Céspedes Martinez, Xavier Serra Ruiz, Virginia Robles, Ernesto Lastiri, Zahira Perez, Elena Oller, Candela Fernandez-Naval, Mónica Martinez-Gallo, Francesc Casellas and Natalia Borruel Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Sat Jul 26 10:55:29 2025 CEST ModDate: Sat Jul 26 11:04:24 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 649194 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZSTIIP+URWPalladioL-Ital Type 1 Custom yes yes yes 105 0 MLTPMG+VnURWPalladioL Type 1 Custom yes yes yes 106 0 UNWJNK+URWPalladioL-Bold Type 1 Custom yes yes yes 107 0 GTKJNS+URWPalladioL-Roma Type 1 Custom yes yes yes 108 0 LRTYNE+CMSY10 Type 1 Builtin yes yes yes 147 0 CUMHZS+EURM10 Type 1 Builtin yes yes yes 164 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 206 0 JCLMNE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 179 0 JCLMNC+PalatinoLinotype TrueType WinAnsi yes yes no 180 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-10-11 03:59:13 CEST RepresentationInformation: cells-14-01156.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-10-10 17:32:15 CEST Size: 649194 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 391 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Materials and Methods Children: Item: Title: Study Population and Data Collection Item: Title: Assessment of Humoral Immune Response Item: Title: Assessment of Cellular Immune Response Item: Title: Clinical Variables in Inflammatory Bowel Disease, Vaccine Effect, and COVID-19 Infection Item: Title: Statistical Analysis Item: Title: Results Children: Item: Title: Humoral Immune Response Item: Title: Cellular Immune Response Item: Title: Discussion Item: Title: Appendix A Item: Title: References Info: Title: Impaired Long-Term Quantitative Cellular Response to SARS-CoV-2 Vaccine in Thiopurine-Treated IBD Patients Author: Luis Mayorga Ayala, Claudia Herrera-deGuise, Juliana Esperalba, Xavier Martinez-Gomez, Elena Céspedes Martinez, Xavier Serra Ruiz, Virginia Robles, Ernesto Lastiri, Zahira Perez, Elena Oller, Candela Fernandez-Naval, Mónica Martinez-Gallo, Francesc Casellas and Natalia Borruel Subject: Background: Studies investigating the long-term cellular immune response to SARS-CoV-2 mRNA vaccines in patients with inflammatory bowel disease (IBD) remain limited, particularly among those receiving immunosuppressive therapy. Methods: We prospectively evaluated humoral and cellular immune responses at short-term (4–6 weeks) and long-term (6–12 months) time points following SARS-CoV-2 mRNA vaccination in patients with IBD receiving anti-TNF agents, thiopurines, or combination therapy. We defined the short-term response as the measurement taken 4–6 weeks after the second vaccine dose and the long-term response as the measurement taken between 6 and 12 months after the first determination. A cohort of healthy controls was included for short-term comparative analysis. Results: At long-term follow-up, quantitative humoral responses were reduced in patients receiving anti-TNF monotherapy. In contrast, a reduced quantitative cellular response was found in the thiopurine (median 0.7 UI/mL, p < 0.05) and anti-TNF combo groups (median 0.4 UI/mL, p < 0.01) compared to anti-TNF monotherapy (median 2.2 UI/mL). Conclusions: There was a robust long-term humoral and cellular response to vaccination, but a diminished quantitative cellular response in patients treated with thiopurines or combo therapy compared to anti-TNF monotherapy. 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