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      Infectome: A platform to trace infectious triggers of autoimmunity

      review-article
      a , b , * , a , c , b , d , e , d
      Autoimmunity Reviews
      Elsevier B.V.
      AMA, anti-mitochondrial antibody, ANA, anti-nuclear antibody, CMV, cytomegalovirus, CSF, cerebrospinal fluid, EBV, Epstein–Barr virus, EWAS, environmental-wide association study, FDR, first degree relatives, GWAS, genome wide association study, HHV6, human herpes virus 6, LC–MS/MS, liquid chromatography–tandem mass spectrometry (LC–MS/MS), MS, multiple sclerosis, IBS, irritable bowel syndrome, PBC, primary biliary cirrhosis, PCR, polymerase chain reaction, PDC, pyruvate dehydrogenase complex, SLE, systemic lupus erythematosus, Autoantibodies, Autoimmunity, Autoimmune disease, Environment, Infection, Immunity, Microbiome

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          Abstract

          The “exposome” is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the “infectome”, which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regard to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the “immunome” and “microbiome” projects.

          Highlights

          ► Genetics and environment are involved in the pathogenesis of autoimmunity. ► The study of individual infectious agents limits our understanding of the pathogenesis of autoimmunity. ► Exposome describes all environmental factors which we are exposed to. ► Infectome is the infectious component of the exposome. ► Investigation of the infectome is a holistic tool for the study of autoimmunity.

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          Most cited references379

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          Multiple Sclerosis

          New England Journal of Medicine, 343(13), 938-952
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            Multiple sclerosis--the plaque and its pathogenesis.

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              Risk alleles for multiple sclerosis identified by a genomewide study.

              Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis. We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis. A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1x10(-4)); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional nonoverlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor alpha gene (IL2RA) were strongly associated with multiple sclerosis (P=2.96x10(-8)), as were a nonsynonymous SNP in the interleukin-7 receptor alpha gene (IL7RA) (P=2.94x10(-7)) and multiple SNPs in the HLA-DRA locus (P=8.94x10(-81)). Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis. Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Contributors
                Journal
                Autoimmun Rev
                Autoimmun Rev
                Autoimmunity Reviews
                Elsevier B.V.
                1568-9972
                1873-0183
                22 December 2012
                May 2013
                22 December 2012
                : 12
                : 7
                : 726-740
                Affiliations
                [a ]Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London, UK
                [b ]Department of Medicine, University of Thessaly Medical School, Thessaly, Mezourlo, Larissa, Greece
                [c ]Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano (MI), Italy
                [d ]The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel
                [e ]Nutritional Sciences Division, King's College School of Medicine, Franklin Wilkins Building, London, UK
                Author notes
                [* ]Corresponding author at: Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London Medical School at King's College London Hospital, Denmark Hill Campus, London SE5 9RS, UK. Tel./fax: + 44 2032993397, + 44 302410555138. dimitrios.bogdanos@ 123456kcl.ac.uk bogdanos@ 123456med.uth.gr
                Article
                S1568-9972(12)00296-0
                10.1016/j.autrev.2012.12.005
                7105216
                23266520
                78798067-7407-4afa-8daa-3fd0ed2b27a7
                Copyright © 2012 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 25 November 2012
                : 12 December 2012
                Categories
                Article

                Immunology
                ama, anti-mitochondrial antibody,ana, anti-nuclear antibody,cmv, cytomegalovirus,csf, cerebrospinal fluid,ebv, epstein–barr virus,ewas, environmental-wide association study,fdr, first degree relatives,gwas, genome wide association study,hhv6, human herpes virus 6,lc–ms/ms, liquid chromatography–tandem mass spectrometry (lc–ms/ms),ms, multiple sclerosis,ibs, irritable bowel syndrome,pbc, primary biliary cirrhosis,pcr, polymerase chain reaction,pdc, pyruvate dehydrogenase complex,sle, systemic lupus erythematosus,autoantibodies,autoimmunity,autoimmune disease,environment,infection,immunity,microbiome

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