Predictive value of epithelial gene expression profiles for response to infliximab in Crohnʼs disease‡

Arijs, Ingrid; Quintens, Roel; Lommel, Leentje Van; Steen, Kristel Van; Hertogh, Gert De; Lemaire, Katleen; Schraenen, Anica; Perrier, Clémentine; Assche, Gert Van; Vermeire, Séverine; Geboes, Karel; Schuit, Frans; Rutgeerts, Paul

doi:10.1002/ibd.21301

Cited by 152 publications

(120 citation statements)

References 19 publications

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“…We were able to characterize robust gene expression differences associated with deep ulcers and enriched pathway associations with oxidative stress and Th1 polarization. These data can serve to direct future therapy for ileal mucosal healing, which may not be achieved with current approaches (12). In contrast, we were able to detect an association between depletion of specific Firmicutes and Bacteroidetes taxa and expansion of Proteobacteria and clinical severity, as measured by the PCDAI.…”

Section: Methodsmentioning

confidence: 56%

“…The use of gene expression or microbial markers to support diagnosis and adjust therapy for specific subsets of IBD is currently limited. In one single-center study, researchers tested for association between ileal or colonic gene expression and subsequent clinical and mucosal response to anti-TNF-α therapy in adults with established CD (12). Overall, 12 of 19 patients experienced healing of colonic ulcers with anti-TNF-α, and baseline expression of specific colonic genes was associated with subsequent response.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Haberman¹,

Tickle²,

Dexheimer³

et al. 2014

J. Clin. Invest.

453

413

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Section: Methodsmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Haberman¹,

Tickle²,

Dexheimer³

et al. 2014

J. Clin. Invest.

453

413

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“…Nevertheless, the tissue sampling and microchip array analysis methods used in the present study yielded results that indicated patterns of gene expression in dogs with CE were broadly similar to those in humans with IBD, including expression of genes regulating immune and inflammatory responses, metabolism, cell proliferation, and epithelial structure and function. 8,[54][55][56][57][58][59][60][61][62] Results of the present study indicated that the expression of multiple genes regulating mucosal inflammation was markedly altered in dogs with CE, compared with that in healthy control dogs. The differential expression of several genes (fatty acid-binding protein 6, metallothionein 1E, claudin 8, matrix metallopeptidase 1, peroxisome proliferator-activated receptor γ, S100 calcium-binding protein G, and solute carrier family 40 member 1) between groups of dogs in the present study indicated that the molecular pathogenesis of CE in dogs may be similar to that in chronic immune-mediated intestinal inflammation in humans with IBD.…”

Section: Discussionmentioning

confidence: 54%

Gene expression in intestinal mucosal biopsy specimens obtained from dogs with chronic enteropathy

Wilke¹,

Nettleton²,

Wymore³

et al. 2012

ajvr

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Objective—To characterize mucosal gene expression in dogs with chronic enteropathy (CE). Animals—18 dogs with CE and 6 healthy control dogs. Procedures—Small intestinal mucosal biopsy specimens were endoscopically obtained from dogs. Disease severity in dogs with CE was determined via inflammatory bowel index scores and histologic grading of biopsy specimens. Total RNA was extracted from biopsy specimens and microchip array analysis (approx 43,000 probe sets) and quantitative reverse transcriptase PCR assays were performed. Results—1,875 genes were differentially expressed between dogs with CE and healthy control dogs; 1,582 (85%) genes were downregulated in dogs with CE, including neurotensin, fatty acid–binding protein 6, fatty acid synthase, aldehyde dehydrogenase 1 family member B1, metallothionein, and claudin 8, whereas few genes were upregulated in dogs with CE, including genes encoding products involved in extracellular matrix degradation (matrix metallopeptidases 1, 3, and 13), inflammation (tumor necrosis factor, interleukin-8, peroxisome proliferator–activated receptor γ, and S100 calcium-binding protein G), iron transport (solute carrier family 40 member 1), and immunity (CD96 and carcinoembryonic antigen–related cell adhesion molecule [CEACAM] 18). Dogs with CE and protein-losing enteropathy had the greatest number of differentially expressed genes. Results of quantitative reverse transcriptase PCR assay for select genes were similar to those for microchip array analysis. Conclusions and Clinical Relevance—Expression of genes encoding products regulating mucosal inflammation was altered in dogs with CE and varied with disease severity. Impact for Human Medicine—Molecular pathogenesis of CE in dogs may be similar to that in humans with inflammatory bowel disease.

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“…Ready access to disease tissue in UC in the form of biopsies from colonoscopy has prompted a number of transcriptomic studies. One study from the Leuven group identifi ed a composite gene expression signature in mucosal biopsies associated with high sensitivity and specifi city for response to infl iximab ( 81 ). Using a similar strategy another study identifi ed a gene signature associated with non-response to medical therapy in UC.…”

Section: Anti-tnf and Anti-integrin Therapymentioning

confidence: 99%

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Lichtenstein¹,

McGovern²

2016

Am J Gastroenterol Suppl

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Biomarkers, radiology fi ndings, and endoscopic studies, together with clinical assessment of patients with infl ammatory bowel disease, can be used to help determine prognosis, assess disease activity, and increasingly to inform treatment decision-making. This article reviews the current "state of the science" regarding the multitude of different tests that can be performed and how these can be used in the clinic to guide management. Initially, when patients present with symptoms suggestive of infl ammatory bowel disease (IBD), standard endoscopic studies and radiographic studies should be performed and the use of combinations of serologic and fecal markers may additionally be incorporated into patient assessment. Once the patient has a formal diagnosis, prognosis should be assessed and serologic evaluation may be used, but in conjunction with endoscopic and radiographic studies. Within the context of evaluating clinical predictors of disease (e.g., disease location, nutritional status, routine blood tests), early mucosal healing has been linked to better outcomes, and failure to heal the mucosa has been associated with poorer outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (e.g., C-reactive protein, fecal calprotectin, lactoferrin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management. Although there is not yet universal adoption of biomarkers to determine treatment choices (e.g., the use of anti-tumor necrosis factor therapy), biomarkers have enabled us to "fi ne tune" treatment of some patients with IBD. Establishing mechanisms of communicating these risks/benefi ts to patients will be a considerable challenge and remains a priority area of research.

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Predictive value of epithelial gene expression profiles for response to infliximab in Crohnʼs disease‡

Abstract: This study identified a 100% accurate predictive gene signature for (non)response to IFX in CDc, whereas no such a predictive gene set could be identified for CDi.

Cited by 152 publications

References 19 publications

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Gene expression in intestinal mucosal biopsy specimens obtained from dogs with chronic enteropathy

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

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