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Irritable Bowel Syndrome


which provides the first line of xenobiotic defense in the intestinal tract.42,43


Expression levels may affect both gut permeability and immune involvement.


TH1L has a regulatory effect on the elongation of many RNA transcripts, including the mRNAs for replication-dependent histones.44 TH1L is also involved in the control of myeloid cell differentiation and proliferation,45


and expression levels may reflect activity of the


immune system. Discussion


The genes in the IBS diagnostic test were identified from a subset of genes that were discovered in an unbiased search for genes with expression levels that differentiate IBD patients from unaffected normals. Finding a diagnostic test for IBS from a gene expression data set established from IBD patients suggests that there are physiologic similarities between the diseases despite the differences in their symptoms and pathology. This suggestion is consistent with the pathophysiological models of both as diseases that involve gut motility, the immune system, and the enteric nervous system. Further research


1. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al., American College of Gastroenterology Task Force on Irritable Bowel Syndrome, An evidence-based position statement on the management of irritable bowel syndrome, Am J Gastroenterol, 2009;104(Suppl. 1):S1–35.


2. Longstreth GF, Thompson WG, Chey WD, et al., Functional bowel disorders, Gastroenterology, 2005;128:580–9.


3. El-Serag HB, Olden K, Bjorkman D, Health related quality of life among persons with irritable bowel syndrome: A systematic review, Aliment Pharmacol Ther, 2002;16:117–85.


4. Talley NJ, Gabriel SE, Harmsen WS, et al., Medical costs in community subjects with irritable bowel syndrome, Gastroenterology, 1995;109:1736–41.


5. Martin R, Barron JJ, Zacker C, Irritable bowel syndrome: toward a cost-effective management approach, Am J Manag Care, 2001;7(8 Suppl.):S268–75.


6. Longstreth GF, Wilson A, Knight K, et al., Irritable bowel syndrome, health care use, and costs: a U.S. managed care perspective, Am J Gastroenterol, 2003;98:600–7.


7. Mertz H, Naliboff B, Munakata J, et al., Altered rectal perception is a biological marker of patients with irritable bowel syndrome, Gastroenterology, 1995;109:40–52.


8. Azpiroz F, Bouin M, Camilleri M, et al., Mechanisms of hypersensitivity in IBS and functional disorders, Neurogastroenterol Motil, 2007;19(1 Suppl.):62–88.


9. Quigley EM, Disturbances of motility and visceral hypersensitivity in irritable bowel syndrome: biological markers or epiphenomenon, Gastroenterol Clin North Am, 2005;34:221–33.


10. Camilleri M, McKinzie S, Busciglio I, et al., Prospective study of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome, Clin Gastroenterol Hepatol, 2008;6:772–81.


11. Dinan TG, Quigley EM, Ahmed SM, et al., Hypothalamic– pituitary–gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?, Gastroenterology, 2006;130:304–11.


12. Sikander A, Rana SV, Prasad KK, Role of serotonin in gastrointestinal motility and irritable bowel syndrome, Clin Chim Acta, 2009;403:47–55.


13. Liebregts T, Adam B, Bredack C, et al., Immune activation in patients with irritable bowel syndrome, Gastroenterology, 2007;132:913–20.


14. Ohman L, Lindmark AC, Isaksson S, et al., B-cell activation in patients with irritable bowel syndrome (IBS), Neurogastroenterol Motil, 2009;21:644–51.


15. Ohman L, Isaksson S, Lindmark AC, et al., T-cell activation in


Although IBS is clearly a disease with many symptoms that are expressed to varying degrees, the discovery of a gene expression pattern shared by this heterogeneous set of patients points to a commonality of the physiologic mechanisms behind the disease. The test described in this article is an important step toward a positive diagnosis of IBS. The laboratory measurement of expression levels of the genes described herein has been reduced in practice to a commercially available clinical diagnostic test in Exagen’s College of American Pathologists (CAP)-accredited clinical laboratory. The gene expression measurements are reported as a single, easy-to-interpret expression index, with the diagnosis dependent on the value of the index relative to a threshold of zero. The test is robust, reliable, and reproducible.


Additional clinical studies are under way to provide further validation of the clinical utility of the test, including studies on non-IBS patients with clinical symptoms similar to IBS, such as celiac disease, dyspepsia, and other functional gastrointestinal diseases. n


patients with irritable bowel syndrome, Am J Gastroenterol, 2009;104:1205–12.


16. Chuong RS, Locke GR 3rd, Zinsmeister AR, et al., Psychological distress and somatic symptoms in community subjects with irritable bowel syndrome, Am J Gastroenterol, 2009;104:1772–9.


17. Spiller RC, Jenkins D, Thornley JP, et al., Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome, Gut, 2000;47:804–11.


18. Wang LH, Fang XC, Pan GZ, Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis, Gut, 2004;53(8):1096–101. Erratum: Gut, 2004;53(9):1390.


19. Spiller R, Garsed K, Postinfectious irritable bowel syndrome, Gastroenterology, 2009;136:1979–88.


20. Yamini D, Pimentel M, Irritable bowel syndrome and small intestinal bacterial overgrowth, J Clin Gastroenterol, 2010;44:672–5.


21. Foxx-Orenstein A, IBS – Review and What’s New, MedGenMed, 2006;8(3):20.


22. Saad RJ, Chey WD, Recent developments in the therapy of irritable bowel syndrome, Expert Opin Investig Drugs, 2008;17(2):117–30.


23. Pimentel M, Lembo A, Chey WD, TARGET Study Group (179 authors), Rifaximin therapy for patients with irritable bowel syndrome without constipation, N Engl J Med, 2011;6:22–32.


24. Longstreth GF, Thompson WG, Chey WD, et al., Functional bowel disorders, Gastroenterology, 2006;130:1480–91.


25. Whitehed WE, Drossman DA, Validation of symptom-based diagnostic criteria for irritable bowel syndrome: a critical review, Am J Gastroenterol, 2010;105:814–20.


26. Spiegel BM, Farid M, Esrailian E, et al., Is irritable bowel syndrome a diagnosis of exclusion?: a survey of primary care providers, gastroenterologists, and IBS experts, Am J Gastroenterol, 2010;105:848–58.


27. Dalrymple J, Bullock I, Diagnosis and management of irritable bowel syndrome in adults in primary care: summary of NICE guidelines, BMJ, 2008;336:556–7.


28. Green PHR, Jabri B, Celiac disease, Lancet, 2003;362:383–90. 29. Kunkel D, Basseri RJ, Makhani MD, et al., Methane on breath testing is associated with constipation: a systematic review and meta-analysis, Dig Dis Sci, 2011;56(6):1612–8.


30. Otten CM, Kok L, Witteman BJ, et al., Diagnostic performance of rapid tests for detection of fecal calprotectin and lactoferrin and their ability to discriminate inflammatory from irritable bowel syndrome, Clin Chem Lab Med, 2008;46:1275–80.


31. Sidhu R, Wilson P, Wright A, et al., Faecal lactoferrin—a novel


test to differentiate between the irritable and inflamed bowel?, Aliment Pharmacol Ther, 2010;31:1365–70.


32. Lembo AJ, Neri B, Tolley J, et al., Use of serum biomarkers in a diagnostic test for irritable bowel syndrome, Aliment Pharmacol Ther, 2009;15;29:834–42.


33. Fang KC, Clinical utilities of peripheral blood gene expression profiling in the management of cardiac transplant patients, J Immunotoxicol, 2007;4:209–17.


34. Paik S, Shak S, Tang G, et al., A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer, N Engl J Med, 2004;351:2817–26.


35. Burczynski ME, Peterson RL, Twine NC, et al., Molecular classification of Crohn’s disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells, J Molec Diagn, 2006;8:51–61.


36. Lacombe F, Exagen Diagnostics, Genomic marker discovery on an Apple Xserve computational cluster, 2005. Available at: http://images.apple.com/science/pdf/Exagen_WP.pdf (accessed 8 June, 2011).


37. Pimentel M, Amichai MM, Chua K, Brahan L, Validating a new genomic test for irritable bowel syndrome, Gastroenterology, 2011;140(5 Suppl. 1):S798


38. Su AI, Wiltshire T, Batalov S, et al., A gene atlas of the mouse and human protein-encoding transcriptomes, Proc Natl Acad Sci USA, 2004;101(16):6062–7.


39. Koçer SS, Djuric PM, Bugallo MF, et al., Transcriptional profiling of putative human epithelial stem cells, BMC Genomics, 2008;9:359.


40. Parseghian MH, Luhrs KA, Beyond the walls of the nucleus: the role of histones in cellular signaling and innate immunity, Biochem Cell Biol, 2006;84:589–604.


41. Arteaga MF, Wang L, Ravid T, et al., An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machinery, Proc Natl Acad Sci USA, 2006;103:11178–83.


42. Canaparo R, Finnström N, Serpe L, et al., Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum, Clin Exp Pharmacol Physiol, 2007;34:1138–44.


43. Pabarcus MK, Hoe N, Sadeghi S, et al., CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases, Arch Biochem Biophys, 2009;483:66–74.


44. Narita T, Yung TM, Yamamoto J, et al., NELF interacts with CBC and participates in 3’ end processing of replication-dependent histone mRNAs, Mol Cell, 2007;26:349–65.


45. Liu W, Shen X, Yang Y, et al., Trihydrophobin 1 is a new negative regulator of A-Raf kinase, J Biol Chem, 2004;279:10167–75.


will be required to examine the involvement of these genes in IBS disease processes.


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US GASTROENTEROLOGY & HEPATOLOGY REVIEW


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