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      Tracing environmental markers of autoimmunity: introducing the infectome

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          Abstract

          We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease. The infectome is a component which spans the whole life and may begin at the earliest stages right up to the time when the first symptoms manifest, and may thus contribute to the understanding of the pathogenesis of autoimmunity at the prodromal/asymptomatic stages. We provide practical examples and research tools as to how we can investigate disease-specific infectomes, using laboratory approaches employed from projects studying the “immunome” and “microbiome”. It is envisioned that an understanding of the infectome and the environmental factors that affect it will allow for earlier patient-specific intervention by clinicians, through the possible treatment of infectious agents as well as other compounding factors, and hence slowing or preventing disease development.

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          Most cited references355

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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
                +302410555138 , +44-2032993397 , dimitrios.bogdanos@kcl.ac.uk , bogdanos@med.uth.gr , http://www.bogdanoslab.com
                Journal
                Immunol Res
                Immunol. Res
                Immunologic Research
                Springer-Verlag (New York )
                0257-277X
                1559-0755
                17 April 2013
                2013
                : 56
                : 2
                : 220-240
                Affiliations
                [1 ]GRID grid.13097.3c, ISNI 0000000123226764, Division of Transplantation Immunology and Mucosal Biology, Institute of Liver Studies, , King’s College London School of Medicine at King’s College Hospital, ; Denmark Hill Campus, London, SE5 9RS UK
                [2 ]GRID grid.410558.d, ISNI 0000000100356670, Department of Medicine, Faculty of Medicine, School of Health Sciences, , University of Thessaly, ; Biopolis, 41110 Larissa, Greece
                [3 ]Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Centre, Rozzano, MI Italy
                [4 ]GRID grid.413795.d, ISNI 0000000121072845, The Zabludowicz Center for Autoimmune Diseases, , Sheba Medical Center, ; Ramat Gan, Israel
                [5 ]GRID grid.13097.3c, ISNI 0000000123226764, Nutritional Sciences Division, , King’s College School of Medicine, ; Franklin Wilkins Building, London, UK
                Article
                8399
                10.1007/s12026-013-8399-6
                7091283
                23592050
                43a4f24d-180c-4baa-aac0-fc4256197577
                © Springer Science+Business Media New York 2013

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Categories
                Etio Pathogenesis of Autoimmunity
                Custom metadata
                © Springer Science+Business Media New York 2013

                autoimmunity,autoimmune disease,environment,infection,immunity,microbiome

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