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Human endogenous retrovirus HERV-K10 implicated in rheumatoid arthritis and systemic lupus erythematosus: potential pathological triggers?

By Paul N. Nelson, M. Shaw, Denise A. Roden, Graham L. Freimanis, Alan M. Nevill and Paul Rylance

Abstract

Abstract is provided here courtesy of Palacky University, Olomouc.Human endogenous retroviruses (HERVs) are a group of integrated RNA viruses within our human genome. Whilst many are regarded as defective, a number possess the potential to generate retroviral products. Indeed HERVs such as those belonging to the HERV-K family\ud produce retroviral particles in the teratocarcinoma cell line GH and the breast cancer cell line T47D. It has been argued that some retroelements may be beneficial to the human host, perhaps conferring a selective advantage, whereas others may be harmful. Furthermore certain HERVs might be involved in the pathogenesis of autoimmune\ud diseases. The precise mechanisms in diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) may include molecular mimicry and superantigen motifs that evoke and augment unwarranted immune responses. The precise mechanisms in diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) may include molecular mimicry and superantigen motifs that evoke and augment unwarranted\ud immune responses. In the RA joint, tissue destruction is evident over time with recruitment of lymphoid and other cells plus the presence of rheumatoid factor that exhibits increased affinity and change in isotype; evidence of an antigen-driven immune response. The precise trigger of\ud course, remains unknown although certain HERVs have been implicated. In a previous study we found evidence for increased expression of HERV-K10 mRNA in patients with RA. Here we have extended this work by investigating the serological expression to HERV-K10 in patients with RA, SLE, osteoarthritis, normals and other inflammatory disease groups. The study utilised a novel peptide ELISA immunoassay using segments of HERV-K10 identified\ud through bioinformatic analysis. In particular, biotinylation of peptides was necessary for serological discrimination\ud between patients. Overall a significant difference (p<0.05) was found for RA patients in terms of antibody activity to\ud HERV-K10. There was also an increased level of antibodies to HERV-K10 in patients with renal lupus although this was below the level of significance. It is possible that\ud HERV-K10 could act as a trigger in RA/SLE through regions of similarity to host proteins. In this case, the immune response to HERV-K10 could lead to collateral\ud damage and pathogenesis of disease

Topics: Human Endogenous Retroviruses, HERVs, Genomics, RNA, Viral, Retroviridae Infections, Autoimmune Diseases, Rheumatoid Arthritis, Systemic lupus erythematosus, Molecular Biology, Arthritis, Rheumatoid
Publisher: Czech Republic: Palacky University, Olomouc: Faculty of Medicine and Dentistry
Year: 2006
OAI identifier: oai:wlv.openrepository.com:2436/30252
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