TY - JOUR
T1 - Are human endogenous retroviruses triggers of autoimmune diseases?
T2 - Unveiling associations of three diseases and viral loci
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 - Bisgaard Jensen, Sara
AU - Bahrami, Shervin
AU - Lajer, Maria
AU - Schmidt, Kathrine L M
AU - Parving, Hans-Henrik
AU - Junker, Peter
AU - Laska, Magdalena Janina
PY - 2016
Y1 - 2016
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.
U2 - 10.1007/s12026-015-8671-z
DO - 10.1007/s12026-015-8671-z
M3 - Journal article
C2 - 26091722
SN - 0257-277X
VL - 64
SP - 55
EP - 63
JO - Immunologic Research
JF - Immunologic Research
IS - 1
ER -