[en] BACKGROUND AND AIMS: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), remain heterogeneous disorders with variable response to biologics. Post-operative recurrence in CD is common despite surgery and prophylactic biotherapies. Understanding the inflammatory mediators associated with recurrence and treatment response could pave the way for personalized strategies. METHODS: We analyzed serum inflammatory protein signatures using proteomics in two prospective cohorts. The REMIND cohort included post-operative CD patients undergoing ileocecal resection with endoscopic assessment at 6 months (M6). Serum samples were collected at surgery and 6 months later. The ELYP cohort consisted of active IBD patients starting new biotherapies (anti-tumor necrosis factor [anti-TNF], ustekinumab, or vedolizumab). Serum samples were collected pre- and post-treatment (Weeks 14 and 52). RESULTS: In the REMIND cohort, proteomic analysis revealed elevated levels of IFN-γ, CXCL9, and MMP-10 in patients with recurrence, with concentrations associated with recurrence severity. Preoperative MMP-10 levels predicted severe recurrence (AUC = 0.70). Under biotherapies, treatment-specific proteins were associated with recurrence: CXCL9 for anti-TNF and OSM/TGFα modules for ustekinumab. In the ELYP cohort, IFN-γ and CXCL9 were significantly elevated in CD compared to UC and associated with disease activity. Early response to anti-TNF treatment (Week 14) was associated with reductions in CXCL9, MMP-10, and OSM, while deep remission (Week 52) correlated with decreases in CXCL9 and OSM. CONCLUSION: Our findings reveal inflammatory blood proteomic signatures associated with post-operative recurrence and biologic treatment failure in IBD. Several key biomarkers were identified. These results support the rationale for personalized approaches, including combination therapies targeting multiple pathways.ClincialTrials.gov number, NCT02693340 and NCT02693340.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Veyssière, Maëva; Université Paris Cité, INSERM U976, Paris, France.
Hammoudi, Nassim ; Université de Paris, INSERM U1342, Institut de Recherche Saint-Louis, Paris, France. ; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France.
Le Bourhis, Lionel; Université de Paris, INSERM U1342, Institut de Recherche Saint-Louis, Paris, France.
Hassid, Déborah; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France.
Bonnet, Joëlle; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France.
Tran Minh, My-Linh; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France.
Baudry, Clotilde; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France.
Gornet, Jean-Marc; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France.
Chardiny, Victor; Université de Paris, INSERM U1342, Institut de Recherche Saint-Louis, Paris, France.
Seksik, Philippe; Department of Gastroenterology, CRSA, Sorbonne Université, INSERM, APHP, Paris Center for Microbiome Medicine (PaCeMM) FHU, Saint-Antoine Hospital, Paris, France.
Nancey, Stéphane; Department of Gastroenterology, CHU de Lyon, Lyon-Sud hospital, Pierre-Benite, France and INSERM U1111-CIRI, Lyon, France.
Carbonnel, Franck; Department of Gastroenterology, Hopitaux Universitaires Bicêtre, AP-HP, Université Paris Saclay, INSERM CESP, Le Kremlin Bicêtre, Paris, France.
Treton, Xavier; Paris IBD Center, Groupe hospitalier privé Ambroise-Pare Hartmann, Neuilly, 92200, France.
Wils, Pauline ; Department of Gastroenterology, Claude Huriez hospital, University of Lille 2, Lille, France.
Buisson, Anthony ; Université Clermont Auvergne, 3iHP, CHU Clermont-Ferrand, Service d'Hépato- Gastroentérologie, Inserm U1071, M2iSH, USC-INRA 2018, Clermont-Ferrand, France.
Boureille, Arnaud; Nantes Université, CHU Nantes, Institut des Maladies de l'Appareil Digestif, Inserm CIC 1413, Nantes, France.
Hébuterne, Xavier; CHU de Nice et Université Côte d'Azur, Nice, France.
Serrero, Mélanie; Department of Gastroenterology, University Hospital of Marseille Nord, Assistance Publique-Hôpitaux de Marseille (AP-HM), University of Aix-Marseille, Marseille, France.
Fumery, Mathurin ; Department of Gastroenterology, Amiens University Hospital et PeriTox, UMR I-01, Université de Picardie Jules Verne, Amiens, France.
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Blanc, Pierre; Service d'hépatogastroentérologie B, Centre Hospitalier Universitaire (CHU) Montpellier et Université de Montpellier, Montpellier, France.
Peyrin-Biroulet, Laurent; Department of Gastroenterology, CHRU Nancy, INSERM NGERE, Université de Lorraine, Vandœuvre-lès-Nancy, F-54500, France.
Bezault, Madeleine; REMIND Study Group.
Soumelis, Vassili ; Université Paris Cité, INSERM U976, Paris, France. ; Owkin France, Paris, 75010, France.
Allez, Matthieu ; Université de Paris, INSERM U1342, Institut de Recherche Saint-Louis, Paris, France. ; Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France. ; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Blood proteomic signatures associated with disease activity in inflammatory bowel diseases.
Publication date :
28 September 2025
Journal title :
Journal of Crohn's and Colitis
ISSN :
1873-9946
eISSN :
1876-4479
Publisher :
Oxford University Press, Oxford, Gb
Volume :
19
Issue :
9
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
FDM201806006069/Helmsley Charitable Trust and La Fondation pour la Recherche Médicale/
Funding text :
This work was supported by the Helmsley Charitable Trust
and La Fondation pour la Recherche Médicale
(FDM201806006069). M.V. received funding support from
the Fondation pour la Recherche Médicale, grant number
SPF201909009302.
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