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