title: Rheumatoid arthritis is associated with IgG antibodies to human endogenous retrovirus gag matrix: a potential pathogenic mechanism of disease?
abstract: OBJECTIVE
  Human endogenous retrovirus (HERV)-K10 has been implicated in the etiology and pathogenesis of rheumatoid arthritis (RA). A secondary immune response to this virus might suggest an antigen-driven response in patients. The Gag region of HERV-K10 could provide a key epitope important for immunological reactivity. We investigated the presence of IgG antibodies to this region and assessed its significance in RA.
  
  
  METHODS
  We determined an antigenic peptide on the matrix segment of HERV-K10 and developed an ELISA system to detect IgG antibodies in patients with RA and controls. The presence of antibodies to the matrix peptide (denoted as MAG1: RIGKELKQAGRKGNI) was correlated with patient details.
  
  
  RESULTS
  On screening patients' serum, we found a significantly higher mean IgG antibody response to MAG1 in 30 patients with RA as compared to 23 patients with inflammatory bowel disease (p = 0.003), 29 patients with osteoarthritis (p = 0.001), and 43 healthy individuals (p = 0.002). Reactivity was not observed to a control peptide possessing a nonhomologous amino acid sequence. On evaluating clinical details with serological activity, no correlation with disease duration (p = 0.128), sex (p = 0.768), or rheumatoid factor status (p = 0.576) was found.
  
  
  CONCLUSIONS
  A significantly elevated IgG antibody response to an HERV-K10 Gag matrix peptide was observed in patients with RA, suggesting that the exposure of HERV-K10 may cause a secondary, antigenic driven immune response in RA.
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital. p.n.nelson@wlv.ac.uk.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Nelson
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Denise
authors.initials: D
authors.lastname: Roden
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Alan
authors.initials: A
authors.lastname: Nevill
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Graham L
authors.initials: GL
authors.lastname: Freimanis
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Trela
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Hora Davari
authors.initials: HD
authors.lastname: Ejtehadi
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Simon
authors.initials: S
authors.lastname: Bowman
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: John
authors.initials: J
authors.lastname: Axford
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Andy M
authors.initials: AM
authors.lastname: Veitch
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Nicola
authors.initials: N
authors.lastname: Tugnet
authors.affiliation: From the Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton; the Royal Wolverhampton National Health Service Trust, New Cross Hospital, Wolverhampton; Birmingham City University; the Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Birmingham; Sir Joseph Hotung Centre for Musculoskeletal Disorders; St. George's University of London; National Health Service Trust, London, United Kingdom.P.N. Nelson, BSc, PhD, DipTLHE; D. Roden, BSc, MSc; A. Nevill, BSc, PhD; G.L. Freimanis, BSc, MSc, PhD; M. Trela, BSc, MSc; H.D. Ejtehadi, BSc, PhD, PGCert, DipHE, Immunology Research Group, Research Institute in Healthcare Sciences, University of Wolverhampton, Birmingham City University; S. Bowman, PhD, FRCP; N. Tugnet, BmedSci, MBCHB, PG CertMedEd, MRCP, Department of Rheumatology, University Hospitals Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital; J. Axford, DSc, MD, FRCP, FRCPCH, Sir Joseph Hotung Centre for Musculoskeletal Disorders, St. George's University of London, National Health Service Trust; A.M. Veitch, BSc, MBBS, MD, FRCP; P.B. Rylance, BSc, MBBS, CertMedEd, FRCP; The Royal Wolverhampton National Health Service Trust, New Cross Hospital.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Rylance
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015683:Gene Products, gag; D007074:Immunoglobulin G
keywords: BIOINFORMATICS; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN ENDOGENOUS RETROVIRUS; RHEUMATOID ARTHRITIS