title: Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci.
abstract: Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte antigens is reported for multiple sclerosis. We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response.
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Alle' 6, 8000, Århus C, Denmark.
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.affiliation: Bioinformatics Research Center, Aarhus University, 8000, Århus C, Denmark.
authors.forename: Palle
authors.initials: P
authors.lastname: Villesen
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Alle' 6, 8000, Århus C, Denmark.
authors.forename: Kari K
authors.initials: KK
authors.lastname: Nissen
authors.affiliation: Department of Rheumatology, Odense University Hospital, 5000, Odense C, Denmark.
authors.forename: Hanne M
authors.initials: HM
authors.lastname: Lindegaard
authors.affiliation: Steno Diabetes Center, 2820, Gentofte, Denmark.|NNF CBMR, University of Copenhagen, 1017, Copenhagen, Denmark.|Faculty of Health, Aarhus University, 8000, Århus C, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Department of Neurology, Aarhus University Hospital, 8000, Århus C, Denmark.
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.affiliation: Steno Diabetes Center, 2820, Gentofte, Denmark.|Faculty of Health, Aarhus University, 8000, Århus C, Denmark.|Nordsjaellands Hospital, 3400, Hillerod, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Alle' 6, 8000, Århus C, Denmark.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.affiliation: Department of Rheumatology, Vejle Hospital, 71000, Vejle, Denmark.
authors.forename: Tove
authors.initials: T
authors.lastname: Lorenzen
authors.affiliation: King Christian 10th Hospital for Rheumatic Diseases, 6300, Graasten, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Alle' 6, 8000, Århus C, Denmark.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Jensen
authors.affiliation: Department of Clinical Medicine, Aarhus University, 8000, Århus C, Denmark.
authors.forename: Shervin
authors.initials: S
authors.lastname: Bahrami
authors.affiliation: Steno Diabetes Center, 2820, Gentofte, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Alle' 6, 8000, Århus C, Denmark.
authors.forename: Kathrine L M
authors.initials: KL
authors.lastname: Schmidt
authors.affiliation: Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, 1017, Copenhagen, Denmark.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.affiliation: Department of Rheumatology, Odense University Hospital, 5000, Odense C, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Alle' 6, 8000, Århus C, Denmark. laska@biomed.au.dk.
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Laska
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000821:virology*; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000821:virology*; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D056426:Genetic Loci; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics / Q000821:virology*; D020641:Polymorphism, Single Nucleotide; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014764:Viral Proteins
keywords: Multiple sclerosis; Rheumatoid arthritis; Single nucleotide polymorphisms; Synergy; Type 1 diabetes mellitus