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      Borrelia infection and risk of celiac disease

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          Abstract

          Background

          Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.

          Methods

          Biopsy reports from all of Sweden’s pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease.

          Results

          Twenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06–2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40–2.35), with the risk of disease being highest in the first year of follow-up.

          Conclusions

          Only a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.

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          Most cited references28

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          Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease

          Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T H 1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pT reg ) conversion and promoting T H 1 immunity to dietary antigen. Initiation of T H 1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pT reg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD.
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            Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study.

            Few studies have assessed the role of specific gastrointestinal infections in celiac disease. We investigated whether increased frequency of rotavirus infection, a common cause of gastrointestinal infection and inflammation, predicts increased risk of celiac disease autoimmunity. A cohort of 1,931 children from the Denver metropolitan area who carried celiac disease human leukocyte antigen (HLA) risk alleles were followed from infancy for development of celiac disease autoimmunity, defined as positivity at two or more subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies measured using a radioimmunoassay with human recombinant tTG. Blood samples were obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus antibodies were assayed using an indirect enzyme immunoassay in serial serum samples from each case and two matched controls. Frequency of infections were estimated by the number of increases (> 2 assay coefficient of variation) in rotavirus antibody between clinic visits. Fifty-four cases developed celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent rotavirus infections predicted a higher risk of celiac disease autoimmunity (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI] 0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for > or = 2 infections, rate ratio for trend per increase in number of infections = 1.94, 95% CI 1.04-3.61, p = 0.037). The result was similar after adjustment for gender, ethnic group, maternal education, breast-feeding, day-care attendance, number of siblings, season of birth, and number of HLA DR3-DQ2 haplotypes. This prospective study provides the first indication that a high frequency of rotavirus infections may increase the risk of celiac disease autoimmunity in childhood in genetically predisposed individuals.
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              The role of infections in autoimmune disease.

              Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.
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                Author and article information

                Contributors
                212 851-4582 , aa819@columbia.edu
                +46-19-6021000 , jonasludvigsson@yahoo.com
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                15 September 2017
                15 September 2017
                2017
                : 15
                : 169
                Affiliations
                [1 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Department of Medicine, , Columbia University Medical Center, ; New York, NY USA
                [2 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Celiac Disease Center, , Columbia University Medical Center, ; New York, NY USA
                [3 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Institute of Human Nutrition, , Columbia University Medical Center, ; New York, NY USA
                [4 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Department of Medical Epidemiology and Biostatistics, , Karolinska Institutet, ; Stockholm, Sweden
                [5 ]ISNI 0000 0001 0728 151X, GRID grid.260917.b, Division of Infectious Diseases, Department of Medicine, , New York Medical College, ; Valhalla, NY USA
                [6 ]ISNI 0000 0001 0123 6208, GRID grid.412367.5, Department of Pediatrics, , Örebro University Hospital, ; Örebro, Sweden
                [7 ]ISNI 0000 0004 1936 8868, GRID grid.4563.4, Division of Epidemiology and Public Health, , School of Medicine, University of Nottingham, ; Nottingham, UK
                Article
                926
                10.1186/s12916-017-0926-1
                5599869
                28911326
                fa2aba5e-d503-4798-a939-5bec66aa104c
                © The Author(s). 2017

                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
                : 28 April 2017
                : 9 August 2017
                Funding
                Funded by: The Swedish Society of Medicine
                Funded by: Swedish Research Council
                Funded by: Swedish Celiac Society
                Funded by: National Institute of Allergy and Infectious Diseases (US)
                Funded by: Global Lyme Alliance
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Medicine
                celiac disease,lyme disease,infection,inflammation,borrelia burgdorferi
                Medicine
                celiac disease, lyme disease, infection, inflammation, borrelia burgdorferi

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