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Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis
  1. Ryan W Gan1,
  2. M Kristen Demoruelle2,
  3. Kevin D Deane2,
  4. Michael H Weisman3,
  5. Jane H Buckner4,
  6. Peter K Gregersen5,
  7. Ted R Mikuls6,
  8. James R O'Dell6,
  9. Richard M Keating7,
  10. Tasha E Fingerlin8,
  11. Gary O Zerbe9,
  12. Michael J Clare-Salzler10,
  13. V Michael Holers2,
  14. Jill M Norris1
  1. 1Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA
  2. 2Division of Rheumatology, University of Colorado, Aurora, Colorado, USA
  3. 3Cedars-Sinai Medical Center, Los Angeles, California, USA
  4. 4Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
  5. 5Feinstein Institute for Medical Research and North Shore-Long Island Jewish Health System, Manhasset, New York, USA
  6. 6Veteran Affairs Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska, USA
  7. 7Scripps Health, La Jolla, California, USA
  8. 8National Jewish Health, Denver, Colorado, USA
  9. 9Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA
  10. 10Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA
  1. Correspondence to
    Dr Jill M Norris, 13001 E. 17th Place, B119, Bldg 500, Room W3141A, Anschutz Medical Campus, Aurora, CO 80045, USA; Jill.Norris{at}


Objectives 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.

  • Autoantibodies
  • Rheumatoid Arthritis
  • Epidemiology

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  • Handling editor Tore K Kvien

  • Contributors RWG and GOZ contributed to the analysis of data. RWG, MKD, KDD, MHW, JHB, PKG, TRM, JRO, RMK, TEF, GOZ, MJC-S, VMH and JMN contributed to the study design and acquisition of data, interpretation of data and results, provided content expertise, and the writing of the manuscript.

  • Funding This work is supported by the NIH Autoimmunity Prevention Center (U19 AI050864, U01 AI101981, and U01 AI101990), the National Institutes of Health (R01 AR051394, M01 RR00069, M01 RR00425, K23 AR051461 and T32 AR007534), the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health, National Center for Research Resources (grant UL1RR033176) and is now at the National Center for Advancing Translational Sciences (grant UL1TR000124), the Walter S. and Lucienne Driskill Foundation, the Research Support Fund grant from the Nebraska Medical Center and the University of Nebraska Medical Center.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study protocol was approved by the following institutional review boards (IRBs) at each SERA site: Colorado Multiple IRB, University of Nebraska Medical Center IRB, Benaroya Research Institute at Virginia Mason IRB, Cedars-Sinai Medical Center's IRB, North Shore-LIJ IRB and the Chicago Biomedicine IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.