Exposure to ambient air pollution and autoantibody status in rheumatoid arthritis
To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status
We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO2, SO2, particulate matter [PM2.5, PM10], and ozone) from air quality monitoring stations at patients’ residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration.
The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM2.5 exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM2.5 exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers.
In an elderly cohort of RA patients, fine particulate matter (PM2.5) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted.
• A study that integrates both genetic and environmental exposure data, relative to RA autoantibody status.
• Of different air pollutants measures, exposure to fine particulate matter (PM2.5) appears to be most closely linked to ACPA titers.
KeywordsAir pollution Autoantibodies Environment Rheumatoid arthritis
anti-cyclic citrullinated peptide antibody
systemic lupus erythematosus
veterans affairs rheumatoid arthritis
particulate matter size (diameter) generally less than 2.5 micrometers (μm)
particulate matter size (diameter) generally less than 10 micrometers (μm)
state or local air monitoring stations
juvenile idiopathic arthritis
Bryant R. England, MD, VA Nebraska-Western Iowa Health Care System and the University of Nebraska Medical Center.
Richard Amdur, PhD, Lead Biostatistician, Medical Faculty Associates, Clinical Professor, Dept. of Surgery, George Washington University School of Medicine & Health Sciences.
Asha Alex: Contributed to the study conception, design, data acquisition, analysis, interpretation of data, drafted and approved the manuscript and agrees to be accountable for my contributions.
Gary Kunkel: Contributed to data acquisition, concept, interpretation of data, reviewed, approved and modified the manuscript and agrees to be accountable for his contributions.
Harlan Sayles: Contributed to the design of the work, data analysis, interpretation of data, approved and modified the final version and agrees to be accountable for his contributions.
Jorge D. Flautero Arcos: Contributed to data acquisition, concept, interpretation of data, reviewed, approved and modified the manuscript and agrees to be accountable for his contributions.
Ted Mikuls: Contributed to study design, data analysis, reviewed, approved and modified the manuscript and agrees to be accountable for his contributions.
Gail S Kerr: Contributed to the study conception, design, interpretation of data, reviewed, modified and approved the manuscript and agrees to be accountable for her contributions.
The Veterans Affairs Rheumatoid Arthritis Registry (VARA) has received funding from: Nebraska Arthritis Outcomes Research Center at the University of Nebraska Medical Center; Veterans Affairs Health Services Research and Development Program of the Veterans Health Administration (HSR&D), Veterans Health Administration (Veterans Affairs Merit award); HSR&D Career Development Award, Grant Number: CDA 07-221. No financial or non-financial conflicts of interest exist for any of the authors.
Compliance with ethical standards
All VARA sites have approval from their respective Institutional Review Boards, as well as by the VARA Scientific Ethics Advisory Committee.
- 2.Stolt P, Bengtsson C, Nordmark B, Lindblad S, Lundberg I, Klareskog L, Alfredsson L, EIRA study group (2003) Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases. Ann Rheum Dis 62:835–841CrossRefGoogle Scholar
- 4.Mikuls TR, Gould KA, Bynoté KK, Yu F, LeVan TD, Thiele GM et al (2010) Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione s-transferase in a cross-sectional study. Arthritis Res Ther 12:R213CrossRefGoogle Scholar
- 5.Lundström E, Källberg H, Alfredsson L, Klareskog L, Padyukov L (2009) Gene-environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: All alleles are important. Arthritis Rheum 60:1597–1603CrossRefGoogle Scholar
- 6.Klareskog L, Stolt P, Lundberg K, Källberg H, Bengtsson C, Grunewald J, Rönnelid J, Harris HE, Ulfgren AK, Rantapää-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L (2006) A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54:38–46CrossRefGoogle Scholar
- 9.Mackie SL, Taylor JC, Twigg S, Martin SG, Steer S, Worthington J, Barton A, Wilson AG, Hocking L, Young A, Emery P, Barrett JH, Morgan AW (2012) Relationship between area-level socio-economic deprivation and autoantibody status in patients with rheumatoid arthritis: multicentre cross-sectional study. Ann Rheum Dis 71:1640–1645CrossRefGoogle Scholar
- 10.Yang G, Bykerk VP, Boire G, Hitchon CA, Thorne JC, Tin D, Haraoui B, Keystone EC, Pope JE, CATCH Investigators (2015) Does socioeconomic status affect outcomes in early inflammatory arthritis? Data from a canadian multisite suspected rheumatoid arthritis inception cohort. J Rheumatol 42:46–54CrossRefGoogle Scholar
- 12.Quinones M, Dowell S, Kerr GS, Swearingen C, Yazici Y, Espinoza L, Garcia-Valladares I, Treadwell EL, Lawrence Ford T, Scherrer Y, Mosley-WIlliams A, Perez Alamino R, Ince A, Amatruda JFAJ (2015) Socioeconomic status, ethnicity/race, and autoantibody status in rheumatoid arthritis. Arthritis Rheumatol 67(Suppl 10)Google Scholar
- 16.Fernandes EC, Silva CA, Braga AL, Sallum AME, Campos LMA, Farhat SCL (2015) Exposure to air pollutants increased disease activity in childhood-onset systemic lupus erythematosus patients. Arthritis Care Res (Hoboken) 67(11):1609–1614Google Scholar
- 17.Bernatsky S, Smargiassi A, Johnson M, Kaplan GG, Barnabe C, Svenson L, Brand A, Bertazzon S, Hudson M, Clarke AE, Fortin PR, Edworthy S, Bélisle P, Joseph L (2015) Fine particulate air pollution, nitrogen dioxide, and systemic autoimmune rheumatic disease in Calgary, Alberta. Environ Res 140:474–478CrossRefGoogle Scholar
- 23.Mikuls TR, Kazi S, Cipher D, Hooker R, Kerr GS, Richards JS et al (2007) The association of race and ethnicity with disease expression in male US veterans with rheumatoid arthritis. J Rheumatol 34Google Scholar