Human Endogenous Retroviral Genetic Element With Immunosuppressive Activity in Both Human Autoimmune Diseases and Experimental Arthritis

Objective. Human endogenous retroviruses (HERVs) are remnants of past retroviral infections in the human genome and have been implicated in different aspects of human biology. The aim of this study was to identify HERVs that are associated with the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE). Methods. The study subjects included 45 female patients with SLE and 50 healthy controls matched for geographic area, age, and sex. Real-time reverse transcription-polymerase chain reaction analysis was used to examine the transcription levels of 11 genes with coding capacity for complete envelope (Env) protein in these individuals. In this way, 1 HERV locus was identified as a potential modulator of autoimmunity. The env gene encoded by this HERV locus was cloned and examined for the ability to express a functional protein with immunosuppressive potential. Results. Expression of the env59 gene was negatively correlated with pathogenetic factors of human autoimmune rheumatic diseases, including such factors as the levels of interleukin-6 (IL-6) and Toll-like receptor 7. This gene was capable of encoding a fully functional Env glycoprotein that was found to contain a domain, the immunosuppressive (ISU) domain, that, when evaluated ex vivo in patients with SLE and those with rheumatoid arthritis as well as in animal models, showed strong antiinflammatory activity, including the ability to lower IL-6 levels. Conclusion. The env59 gene has been adapted by the immune system as a control mechanism in autoimmunity. The peptides derived from the ISU domain contained in the Env59 protein may be useful as potentially new biologic treatments in rheumatic diseases such as SLE.