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Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease.

ABSTRACT: BACKGROUND:With the changed therapeutic armamentarium for Crohn's disease (CD) and ulcerative colitis (UC), biomarkers predicting treatment response are urgently needed. We studied whole blood and mucosal expression of genes previously reported to predict outcome to anti-TNF therapy, and investigated if the signature was specific for anti-TNF agents. METHODS:We prospectively included 54 active IBD patients (24CD, 30UC) initiating anti-TNF therapy, as well as 22 CD patients initiating ustekinumab and 51 patients initiating vedolizumab (25CD, 26UC). Whole blood expression of OSM, TREM1, TNF and TNFR2 was measured prior to start of therapy using qPCR, and mucosal gene expression in inflamed biopsies using RNA-sequencing. Response was defined as endoscopic remission (SES-CD???2 at week 24 for CD and Mayo endoscopic sub-score???1 at week 10 for UC). FINDINGS:Baseline whole blood TREM1 was downregulated in future anti-TNF responders, both in UC (FC?=?0.53, p?=?.001) and CD (FC?=?0.66, p?=?.007), as well as in the complete cohort (FC?=?0.67, p?

SUBMITTER: Verstockt B

PROVIDER: S-EPMC6413341 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease.

Verstockt Bram B Verstockt Sare S Dehairs Jonas J Ballet Vera V Blevi Helene H Wollants Willem-Jan WJ Breynaert Christine C Van Assche Gert G Vermeire Séverine S Ferrante Marc M

EBioMedicine 20190124

<h4>Background</h4>With the changed therapeutic armamentarium for Crohn's disease (CD) and ulcerative colitis (UC), biomarkers predicting treatment response are urgently needed. We studied whole blood and mucosal expression of genes previously reported to predict outcome to anti-TNF therapy, and investigated if the signature was specific for anti-TNF agents.<h4>Methods</h4>We prospectively included 54 active IBD patients (24CD, 30UC) initiating anti-TNF therapy, as well as 22 CD patients initiat ...[more]

PMID: 30685385

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Project description:BackgroundPersonalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.AimTo identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.MethodsWe performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis.ResultsA functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.ConclusionsThere are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

Dataset Information

Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease.

Publications

Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease.

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