title: Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis.
abstract: OBJECTIVE
  Type I IFNs have recently been implicated in autoantibody-mediated diseases such as SLE. As half the RA patients display a type I IFN(high) signature, we investigated in a pilot study if type I IFN determines the autoantibody response in RA.
  
  
  METHODS
  Serum and peripheral blood cells were obtained from 52 RA patients, with paired samples before and after infliximab treatment in 21 patients. Additional samples were collected from 8 anti-citrullinated protein antibody (ACPA)-positive individuals without arthritis and from 10 ACPA-negative healthy controls. The type I IFN signature was determined by peripheral blood cell gene expression analysis and quantitative RT-PCR. ACPA IgG and IgM, RF IgM, anti-nucleosome IgM and anti-dsDNA were measured by ELISA.
  
  
  RESULTS
  The type I IFN signature was not related to the presence and titers of ACPA and RF during active disease. TNF blockade induced a similar rise of ANAs, and a similar decrease in RF titers in both groups. ACPA IgG and IgM levels appeared to be down-modulated only in the type I IFN(low) group. These changes were independent of the changes in type I IFN response gene activity after TNF blockade. Furthermore, the ACPA response in individuals without arthritis and inflammation was not related to an increase of type I IFN.
  
  
  CONCLUSIONS
  In this explorative study, type I IFN signature does not appear to have a major impact on the humoral autoimmune response in RA. Replication of these data remains warranted.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Tineke
authors.initials: T
authors.lastname: Cantaert
authors.forename: Lisa G
authors.initials: LG
authors.lastname: van Baarsen
authors.forename: Carla A
authors.initials: CA
authors.lastname: Wijbrandts
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Thurlings
authors.forename: Marleen G
authors.initials: MG
authors.lastname: van de Sande
authors.forename: Carina
authors.initials: C
authors.lastname: Bos
authors.forename: Tineke C T M
authors.initials: TC
authors.lastname: van der Pouw Kraan
authors.forename: Tineke Kraan
authors.initials: TK
authors.lastname: van der Pouw
authors.forename: Cor L
authors.initials: CL
authors.lastname: Verweij
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Baeten
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D007370:Interferon Type I / Q000235:genetics*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012217:Rheumatoid Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D000069285:Infliximab