Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci

Bjørn A Nexø; Palle Villesen; Kari K Nissen; Hanne M Lindegaard; Peter Rossing; Thor Petersen; Lise Tarnow; Bettina Hansen; Tove Lorenzen; Kim Hørslev-Petersen; Sara B Jensen; Shervin Bahrami; Maria Lajer; Kathrine L M Schmidt; Hans-Henrik Parving; Peter Junker; Magdalena J Laska

doi:10.1007/s12026-015-8671-z

Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci

Bjørn A Nexø, Palle Villesen, Kari K Nissen, Hanne M Lindegaard, Peter Rossing, Thor Petersen, Lise Tarnow, Bettina Hansen, Tove Lorenzen, Kim Hørslev-Petersen, Sara B Jensen, Shervin Bahrami, Maria Lajer, Kathrine L M Schmidt, Hans-Henrik Parving, Peter Junker, Magdalena J Laska

Institut for Klinisk Medicin

25 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Immunologic Research
Vol/bind	64
Udgave nummer	1
Sider (fra-til)	55-63
Antal sider	9
ISSN	0257-277X
DOI	https://doi.org/10.1007/s12026-015-8671-z
Status	Udgivet - 1 feb. 2016

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10.1007/s12026-015-8671-zLicens: CC BY

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Nexø, B. A., Villesen, P., Nissen, K. K., Lindegaard, H. M., Rossing, P., Petersen, T., Tarnow, L., Hansen, B., Lorenzen, T., Hørslev-Petersen, K., Jensen, S. B., Bahrami, S., Lajer, M., Schmidt, K. L. M., Parving, H-H., Junker, P., & Laska, M. J. (2016). Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci. Immunologic Research, 64(1), 55-63. https://doi.org/10.1007/s12026-015-8671-z

Nexø, BA, Villesen, P, Nissen, KK, Lindegaard, HM, Rossing, P, Petersen, T, Tarnow, L, Hansen, B, Lorenzen, T, Hørslev-Petersen, K, Jensen, SB, Bahrami, S, Lajer, M, Schmidt, KLM, Parving, H-H, Junker, P & Laska, MJ 2016, 'Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci', Immunologic Research, bind 64, nr. 1, s. 55-63. https://doi.org/10.1007/s12026-015-8671-z

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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.",

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AU - Nexø, Bjørn A

AU - Villesen, Palle

AU - Nissen, Kari K

AU - Lindegaard, Hanne M

AU - Rossing, Peter

AU - Petersen, Thor

AU - Tarnow, Lise

AU - Hansen, Bettina

AU - Lorenzen, Tove

AU - Hørslev-Petersen, Kim

AU - Jensen, Sara B

AU - Bahrami, Shervin

AU - Lajer, Maria

AU - Schmidt, Kathrine L M

AU - Parving, Hans-Henrik

AU - Junker, Peter

AU - Laska, Magdalena J

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N2 - 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.

AB - 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.

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Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci

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