Dataset Information

External validation of serum biomarkers predicting short-term and mid/long-term relapse in Crohn’s disease patients stopping infliximab

ABSTRACT: Background and aims: In Crohn’s disease (CD) patients on combination therapy (infliximab and immunosuppressant) and stopping infliximab (STORI cohort), the risk of short-term (<6 months) and mid/long-term relapse (>6 months) was associated with specific blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort. Methods: The SPARE trial included patients with CD in sustained steroid-free clinical remission, on combination therapy and randomly allocated to one of three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. As it was performed in STORI, 202 immune-related proteins were measured in the baseline serum of SPARE (arm stopping infliximab, n=63-67). The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The external validation of biomarkers (individually and combined by pairs) was evaluated by a discrimination analysis (c-statistic) and compared to CRP, faecal calprotectin and a previously validated model (CEASE). Results: In STORI and SPARE, specific blood protein profiles were associated with the risk of short-term (eg, high level: CRP, HP, IL6, CLEC4C, 3.5

ORGANISM(S): Homo Sapiens

SUBMITTER: Nicolas Pierre

PROVIDER: PXD051233 | panorama | Sat Aug 31 00:00:00 BST 2024

REPOSITORIES: PanoramaPublic

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External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab.

Pierre Nicolas N Huynh-Thu Vân Anh VA Baiwir Dominique D Mazzucchelli Gabriel G Fléron Maximilien M Trzpiot Lisette L Eppe Gauthier G De Pauw Edwin E Laharie David D Satsangi Jack J Bossuyt Peter P Vuitton Lucine L Vieujean Sophie S Colombel Jean-Frédéric JF Meuwis Marie-Alice MA Louis Edouard E

Gut 20241111 12

<h4>Objective</h4>In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A p ...[more]

PMID: 39134391

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Project description:The current treatment for Celiac Disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in faecal samples may improve and facilitate non-invasive clinical management of CD on GFD. For this purpose, faecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In the present observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) subjects and 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 adult healthy individuals and from a cohort of 19 untreated paediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA, other sncRNA (piRNA and tRNA) and microbiota profiles were altered in tCD subjects(adj.p<0.05). Findings were validated in one external group of controls. In tCD-TG-, GFD duration correlated with five miRNA levels (p<0.05): for miR-4533-3p and miR-2681-3p, the longer the diet adherence, the less the expression differed from controls. tCD-TG+ and untreated paediatric CD patients showed a similar miRNA dysregulation. Immune-response, trans-membrane transport and cell death pathways were enriched in targets of identified miRNAs. Bifidobacterium longum, Ruminococcus bicirculans and Haemophilus parainfluenzae abundances shifted (adj. p<0.05) with a progressive reduction of denitrification pathways with GFD length. Integrative analysis highlighted 121 miRNA-bacterial relationships (adj.p<0.05). Specific faecal sncRNA and microbial patterns characterise CD subjects on GFD, reflecting either the long-term effects or the gut inflammatory status, in case of a not strict/short-time adherence. Our findings suggest novel host-microbial interplays and could help the discovery of biomarkers for the clinical monitoring of GFD over time.

Dataset Information

External validation of serum biomarkers predicting short-term and mid/long-term relapse in Crohn’s disease patients stopping infliximab

Publications

External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab.

Similar Datasets

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