title: Isotypes of Epstein-Barr virus antibodies in rheumatoid arthritis: association with rheumatoid factors and citrulline-dependent antibodies.
abstract: In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by enzyme-linked immunosorbent assays (ELISA). Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs, IgG) and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection). Notably, for IgM and IgA (but not IgG), these were associated with the presence of characteristic RA autoantibodies.
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Marie Wulff
authors.initials: MW
authors.lastname: Westergaard
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Anette Holck
authors.initials: AH
authors.lastname: Draborg
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Troelsen
authors.affiliation: Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.affiliation: Department of Autoimmunology and Biomarkers, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D002956:Citrulline / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C033305:Epstein-Barr virus early antigen; D007132:Immunoglobulin Isotypes; D002956:Citrulline; D012217:Rheumatoid Factor; C417029:EBV-encoded nuclear antigen 1; D008727:Methotrexate