title: Serum cytokine profile of unaffected first-degree relatives of patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Various cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA) and it is known that elevations in multiple cytokines occur prior to disease onset. The objective of our study is to determine whether the cytokine profile in unaffected first-degree relatives (FDR) of patients with RA is distinct from healthy controls.
  
  
  METHODS
  The sera of patients with RA, their unaffected FDR, and healthy controls were measured for 27 cytokines using a luminex-based multiplexed immunoassay. Subjects were also tested for rheumatoid factor and 6 different anticitrullinated protein/peptide antibodies (ACPA). Discriminant analysis was performed to define the cytokine profile of the 3 study groups.
  
  
  RESULTS
  Fourteen patients with RA, 37 unaffected FDR, and 27 healthy controls were enrolled. All patients with RA and 49% of FDR were ACPA-positive. Patients with RA had elevated levels of inflammatory cytokines compared to FDR and controls. Lower interleukin 13 (IL-13) levels were independently associated with RA. IL-4 was significantly lower in FDR compared to controls. Using discriminant analysis based on the levels of all cytokines measured, RA, FDR, and healthy controls could be distinguished with 91% accuracy. ACPA-positive subjects had higher levels of IL-9, but lower levels of IL-12p70 and macrophage inflammatory protein-1β. No individual cytokine was associated with ACPA-positivity in FDR, but the entire cytokine profile accurately distinguished ACPA-positive from ACPA-negative FDR.
  
  
  CONCLUSIONS
  The cytokine profiles of patients with RA, healthy controls, unaffected ACPA-positive FDR, and ACPA-negative FDR appear to be distinct.
authors.affiliation: From the Department of Medicine, Division of Rheumatology, the Department of Microbiology and Immunology, and the Centre for Human Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Lillian
authors.initials: L
authors.lastname: Barra
authors.forename: Kelly
authors.initials: K
authors.lastname: Summers
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Ewa
authors.initials: E
authors.lastname: Cairns
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D010456:Peptides, Cyclic; D012217:Rheumatoid Factor
keywords: ANTICITRULLINATED PROTEIN ANTIBODIES; CYTOKINES; FIRST-DEGREE RELATIVE; RHEUMATOID ARTHRITIS