title: Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis.
abstract: OBJECTIVE
  Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity.
  
  
  METHODS
  The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case-control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier.
  
  
  RESULTS
  In the case-control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2.
  
  
  CONCLUSIONS
  The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA.
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Gan
authors.affiliation: Division of Rheumatology, University of Colorado, Aurora, Colorado, USA.
authors.forename: M Kristen
authors.initials: MK
authors.lastname: Demoruelle
authors.affiliation: Division of Rheumatology, University of Colorado, Aurora, Colorado, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
authors.forename: Jane H
authors.initials: JH
authors.lastname: Buckner
authors.affiliation: Feinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.affiliation: Veteran Affairs Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
authors.affiliation: Veteran Affairs Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: O'Dell
authors.affiliation: Scripps Health, La Jolla, California, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Keating
authors.affiliation: National Jewish Health, Denver, Colorado, USA.
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA.
authors.forename: Gary O
authors.initials: GO
authors.lastname: Zerbe
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clare-Salzler
authors.affiliation: Division of Rheumatology, University of Colorado, Aurora, Colorado, USA.
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002462:Cell Membrane / Q000737:chemistry; D019587:Dietary Supplements; D000939:Epitopes / Q000276:immunology*; D004912:Erythrocytes / Q000737:chemistry; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000032:analysis / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011446:Prospective Studies; D065840:Protective Factors; D012217:Rheumatoid Factor / Q000276:immunology*; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D015525:Fatty Acids, Omega-3; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
keywords: Autoantibodies; Epidemiology; Rheumatoid Arthritis