title: Human endogenous retrovirus-R Env glycoprotein as possible autoantigen in autoimmune disease.
abstract: It has long been discussed whether endogenous retroviruses (ERVs) are involved in the pathogenesis of autoimmune diseases. Among various human endogenous retroviruses (HERVs), we have focused on HERV-R. To investigate the biological roles of HERV-R, we earlier established transgenic rats carrying the full sequence of the viral genome. In these HERV-R rats, however, no disease occurred. Another trigger that induces autoimmunity may be essential for the recognition of HERV-R products by the immune system. Thus, in this study, we mated HERV-R rats with env-pX rats (transgenic rats carrying the env-pX gene of human T cell leukemia virus type I) that develop autoimmune diseases, and generated double transgenic (DTG) rats. In DTG rats, autoimmune diseases occurred similarly in env-pX rats. Interestingly, deposition of rat IgM but not IgG was observed on the glomerular endothelial cells. Such IgM deposition was never seen in the parental HERV-R or env-pX rats. We considered that in situ formation of immune complexes consisted of the HERV-R env glycoprotein and anti-HERV-R env IgM antibodies (Abs) in DTG rats, according to the following evidence: (1) No dense deposit, representing deposition of circulating immune complexes, was seen on glomerular endothelial cells. (2) IgM Abs reactive with HERV-R env glycoprotein were generated in the serum. (3) HERV-R env glycoprotein was expressed in the kidney, specifically on glomerular endothelial cells. (4) IgM deposition was partly colocalized with the HERV-R env glycoprotein on the glomeruli. These findings strongly suggest that the HERV-R env glycoprotein is recognized as an autoantigen in the host with autoimmune diseases.
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-0812, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sasaki
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Chihiro
authors.initials: C
authors.lastname: Iinuma
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Katsumata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Otsuka
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology*; D020077:Endogenous Retroviruses / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology; D051381:Rats; D055647:Rats, Transgenic; D016019:Survival Analysis
chemical_list: D001324:Autoantigens; D015686:Gene Products, env; D007075:Immunoglobulin M