Exposure to ambient air pollution and autoantibody status in rheumatoid arthritis

  • Asha M. Alex
  • Gary Kunkel
  • Harlan Sayles
  • Jorge D. Flautero Arcos
  • Ted R. Mikuls
  • Gail S. KerrEmail author
Original Article



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.

Key Points

• 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.


Air pollution Autoantibodies Environment Rheumatoid arthritis 



air pollutants


rheumatoid Arthritis


shared epitope


rheumatoid factor


anti-cyclic citrullinated peptide antibody


systemic lupus erythematosus


veterans affairs rheumatoid arthritis


veterans affairs


nitrogen dioxide


sulfur dioxide


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


socioeconomic status


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.

Authors’ contributions

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.

Funding information

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.




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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.RheumatologyMedStar Georgetown University HospitalWashingtonUSA
  2. 2.RheumatologyDC VA Medical CenterWashingtonUSA
  3. 3.Rheumatology, Clinic 2University of Utah HospitalSalt Lake CityUSA
  4. 4.Department of BiostatisticsUniversity of Nebraska Medical CenterOmahaUSA
  5. 5.RheumatologyHoward UniversityWashingtonUSA

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