title: Association of anticytomegalovirus seropositivity with more severe joint destruction and more frequent joint surgery in rheumatoid arthritis.
abstract: OBJECTIVE
  Expansion of autoreactive CD4+CD28(null)  T cells is associated with extraarticular disease manifestations, including rheumatoid vasculitis, and it has recently been demonstrated that expansion of these T cells is associated with anticytomegalovirus (anti-CMV) seropositivity. This study was undertaken to investigate a possible link between latent CMV infection and rheumatoid arthritis (RA).
  
  
  METHODS
  In a retrospective analysis, anti-CMV antibodies and clinical, serologic, and radiologic parameters of joint destruction were examined in 202 RA patients and 272 healthy controls. In addition, frequencies of CD4+CD28(null)  T cells; concentrations of the cytokines monocyte chemotactic protein 1 (MCP-1), interferon-α (IFNα), and IFN-inducible protein 10; and anti-CMV-specific T cell responses were analyzed in RA patients.
  
  
  RESULTS
  Overall, no significant difference in the frequency of anti-CMV seropositivity between RA patients and healthy controls was observed. Among individuals older than age 55 years, however, anti-CMV IgG antibodies were significantly more frequent in RA patients than controls (65.3% and 54.7%, respectively; P = 0.05). Anti-CMV seropositivity in RA patients was associated with an increased frequency of CD4+CD28(null)  T cells and increased serum concentrations of MCP-1. The frequency of anti-CMV-specific CD4+ T cells producing IFNγ was increased in RA patients compared to controls. Most importantly, anti-CMV-seropositive RA patients showed radiographic evidence of more advanced joint destruction and had increased frequencies of joint-related surgical procedures, indicating more severe joint disease.
  
  
  CONCLUSIONS
  Our findings indicate that latent CMV infection aggravates the clinical course of RA and is associated with increased frequencies of CD4+CD28(null)  T cells and of CMV-specific IFNγ-secreting CD4+ T cells.
authors.affiliation: University of Leipzig, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pierer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rothe
authors.forename: Dagmar
authors.initials: D
authors.lastname: Quandt
authors.forename: Anett
authors.initials: A
authors.lastname: Schulz
authors.forename: Manuela
authors.initials: M
authors.lastname: Rossol
authors.forename: Roger
authors.initials: R
authors.lastname: Scholz
authors.forename: Christoph
authors.initials: C
authors.lastname: Baerwald
authors.forename: Ulf
authors.initials: U
authors.lastname: Wagner
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018932:Chemokine CCL2 / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D018106:CD28 Antigens; D018932:Chemokine CCL2