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Increased inflammatory state in IBD multiplex first-degree relatives not developing intestinal disease
  1. Bram Verstockt1,2,
  2. Maaike Vancamelbeke2,
  3. Séverine Vermeire1,2
  1. 1Department of Gastroenterology and Hepatology, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium
  2. 2Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Flanders, Belgium
  1. Correspondence to Professor Bram Verstockt, Department of Gastroenterology and Hepatology, KU Leuven University Hospitals Leuven, Leuven, 3000, Belgium; bram.verstockt{at}

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With great interest, we read the recent publication by the GEM Project Research Consortium on proteomic immune responses and barrier dysfunction signatures in the preclinical phase of Crohn’s disease (CD).1 Out of 446 individual proteins (including 92 from the OLINK inflammation panel), the authors identified 25 serum proteins significantly associated with the future development of CD in a nested case-control cohort of 355 first-degree relatives (FDRs) of patients with inflammatory bowel diseases (IBDs). Besides CXCL9 as the top protein with the largest effect size related to CD onset, the proteomic signature included various other proteins—such as TREM1 and OSM—from which the encoding genes have been implicated in IBD pathogenesis.2–4

Similarly, we previously recruited 20 multiple affected IBD families with ≥3 first-degree members with IBD, totalling 51 patients with IBD (38 patients with CD and 13 ulcerative colitis (UC)) and 39 age-matched and gender-matched FDR (median (IQR) age 45.5 (29.4–58.4) years) (online supplemental table 1). We also collected 42 age-matched and gender-matched healthy individuals (HC) belonging to eight control families without any IBD or other immune-mediated disease involvement. Families were followed up until June 2023, resulting in a median follow-up of 8.1 (8.1–8.2) years, in contrast to a medium follow-up of 2 years in the current GEM report. Most patients with IBD (82.3%) had a faecal calprotectin <250 µg/g at inclusion, indicating quiescent disease. Small intestinal permeability was assessed using the lactulose-mannitol urine test. Faecal calprotectin was measured using the Bühlmann fCal ELISA kit, while 92 serum proteins were measured using the OLINK proximity extension technology …

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  • Contributors MV contributed to data acquisition, statistical analysis and results interpretation. BV contributed to statistical analysis, results interpretation and drafting of the manuscript. SV and BV contributed to study design, patient recruitment and assessment, results interpretation and critical revision of the manuscript. All authors agreed with the final version of the manuscript prior to submission.

  • Funding BV is supported by the Clinical Research Fund (KOOR) at the University Hospitals Leuven and the Research Council at the KU Leuven. SV holds a BOF-Fundamental Clinical Research Mandate from the KU Leuven.

  • Competing interests SV has received grants from AbbVie, J&J, Pfizer, Galapagos and Takeda; consulting and/or speaking fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG and Zealand Pharma. BV has received research support from AbbVie, Biora Therapeutics, Landos, Pfizer, Sossei Heptares and Takeda; Speaker’s fees from Abbvie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Eli Lily, Falk, Ferring, Galapagos, Janssen, MSD, Pfizer, R-Biopharm, Takeda, Truvion and Viatris; Consultancy fees from Abbvie, Alimentiv, Applied Strategic, Atheneum, Biora Therapeutics, Bristol Myers Squibb, Eli Lily, Galapagos, Guidepont, Landos, Mylan, Inotrem, Ipsos, Janssen, Progenity, Sandoz, Sosei Heptares, Takeda, Tillots Pharma and Viatris. MV does not report any COI.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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