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      Plasma levels of TNF-α, IL-6, IFN-γ, IL-12, IL-17, IL-22, and IL-23 in achalasia, eosinophilic esophagitis (EoE), and gastroesophageal reflux disease (GERD)

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          Abstract

          Abstract

          An elevation of serum inflammatory biomarkers in achalasia patients compared with controls recently was demonstrated. It has not been determined whether the elevation of inflammatory cytokines is unique to achalasia or occurs with other diseases involving the esophagus. The primary aim of our study was to compare the differences in plasma immunological profiles (TNF- α receptor, IL-6, IFN-γ, IL-12, IL-17, IL-22, and IL-23) of patients with achalasia, eosinophilic esophagitis (EoE), and gastroesophageal reflux disease (GERD). A secondary aim of this study was to classify these same plasma cytokine profiles in the three achalasia subtypes.

          Methods

          Plasma from 53 patients with achalasia, 22 with EoE, and 20 with GERD (symptoms plus esophagitis or + reflux study) were analyzed. Exclusion criteria: malignancy, autoimmune condition, immunodeficiency disorder, and treatment with steroids/immune modulating drugs. Cytokine levels were assayed via multiplex enzyme-linked immunosorbent assay (ELISA).

          Results

          Our key finding revealed significant elevations in IL- 6 ( p = 0.0158) in achalasia patients compared with EoE patients. Overall, plasma inflammatory biomarker patterns were not different in the three subtypes of achalasia.

          Conclusion

          There were no differences between the cytokine levels of any of the measured biomarkers between the achalasia and GERD groups suggesting that luminal stasis does increase biomarker levels for any of the cytokines examined in our study. While these results are an early first step towards clarifying some aspects of the pathogenesis of achalasia, they bring about many more questions that require further investigation and expansion. Further investigation with a larger cohort and a broader panel of biomarkers is needed.

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          Most cited references19

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          Novel p19 Protein Engages IL-12p40 to Form a Cytokine, IL-23, with Biological Activities Similar as Well as Distinct from IL-12

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            ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).

            Esophageal eosinophilia and eosinophilic esophagitis (EoE) are increasingly recognized and prevalent conditions, which now represent common clinical problems encountered by gastroenterologists, pathologists, and allergists. The study of EoE has become a dynamic field with an evolving understanding of the pathogenesis, diagnosis, and treatment. Although there are limited data supporting management decisions, clinical parameters are needed to guide the care of patients with eosinophilic-esophageal disorders. In this evidence-based review, recommendations developed by adult and pediatric gastroenterologists are provided for the evaluation and management of these patients. New terminology is emphasized, particularly the concepts of esophageal eosinophilia and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) as entities distinct from EoE.
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              Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut.

              Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                336-713-7291 , sbclayto@wakehealth.edu , sbclayto@wakeforest.edu
                elliot.cauble@gmail.com
                akumar1@health.usf.edu
                nirav.patil15@gmail.com
                dledford@health.usf.edu
                nkollipu@health.usf.edu
                virellam@musc.edu
                castell@musc.edu
                jrichte1@health.usf.edu
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                11 February 2019
                11 February 2019
                2019
                : 19
                : 28
                Affiliations
                [1 ]ISNI 0000 0004 0459 1231, GRID grid.412860.9, Wake Forest Baptist Medical Center, ; Winston-Salem, NC USA
                [2 ]ISNI 0000 0001 2353 285X, GRID grid.170693.a, University of South Florida, Division of Gastroenterology, ; Florida, USA
                [3 ]ISNI 0000 0004 0406 7499, GRID grid.413319.d, Greenville Health System, ; Greenville, SC USA
                [4 ]ISNI 0000 0001 2353 285X, GRID grid.170693.a, University of South Florida, Division of Allergy Immunology, ; Florida, USA
                [5 ]ISNI 0000 0001 2189 3475, GRID grid.259828.c, Medical University of South Carolina, Division of Endocrinology, ; Charleston, SC USA
                [6 ]ISNI 0000 0001 2189 3475, GRID grid.259828.c, Medical University of South Carolina, Division of Gastroenterology, ; Charleston, SC USA
                Author information
                http://orcid.org/0000-0002-0492-6201
                Article
                937
                10.1186/s12876-019-0937-9
                6371504
                30744559
                d700ed04-6108-4674-b40d-6d3992640319
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 August 2018
                : 22 January 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Gastroenterology & Hepatology
                achalasia,eosinophilic esophagitis,gerd,inflammatory cytokines,il-6
                Gastroenterology & Hepatology
                achalasia, eosinophilic esophagitis, gerd, inflammatory cytokines, il-6

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