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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

Abstract

Objective

To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status

Methods

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.

Results

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.

Conclusions

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.

Keywords

Air pollution Autoantibodies Environment Rheumatoid arthritis 

Abbreviations

AP

air pollutants

RA

rheumatoid Arthritis

SE

shared epitope

RF

rheumatoid factor

ACPA

anti-cyclic citrullinated peptide antibody

SLE

systemic lupus erythematosus

VARA

veterans affairs rheumatoid arthritis

VA

veterans affairs

NO2

nitrogen dioxide

SO2

sulfur dioxide

PM2.5

particulate matter size (diameter) generally less than 2.5 micrometers (μm)

PM10

particulate matter size (diameter) generally less than 10 micrometers (μm)

SLAMS

state or local air monitoring stations

SES

socioeconomic status

JIA

juvenile idiopathic arthritis

Notes

Acknowledgements

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.

Disclosures

None.

References

  1. 1.
    Costenbader KH, Feskanich D, Mandl LA, Karlson EW (2006) Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med 119:503.e1-9CrossRefGoogle Scholar
  2. 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
  3. 3.
    Farhat SCL, Silva CA, Orione MAM, Campos LMA, Sallum AME, Braga ALF (2011) Air pollution in autoimmune rheumatic diseases: a review. Autoimmun Rev 11:14–21CrossRefGoogle Scholar
  4. 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. 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. 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
  7. 7.
    Tobón GJ, Youinou P, Saraux A (2010) The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. J Autoimmun 35:10–14CrossRefGoogle Scholar
  8. 8.
    Joo SH, Lee J, Hutchinson D, Song YW (2019) Prevalence of rheumatoid arthritis in relation to serum cadmium concentrations: cross-sectional study using Korean National Health and Nutrition Examination Survey (KNHANES) data. BMJ Open 9:e023233CrossRefGoogle Scholar
  9. 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. 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
  11. 11.
    Putrik P, Ramiro S, Keszei AP, Hmamouchi I, Dougados M, Uhlig T et al (2015) Lower education and living in countries with lower wealth are associated with higher disease activity in rheumatoid arthritis: results from the multinational COMORA study. Ann Rheum Dis 75(3):540–546CrossRefGoogle Scholar
  12. 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
  13. 13.
    Lewtas J (2007) Air pollution combustion emissions: characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutat Res Mutat Res 636:95–133CrossRefGoogle Scholar
  14. 14.
    Kaplan GG, Hubbard J, Korzenik J, Sands BE, Panaccione R, Ghosh S, Wheeler AJ, Villeneuve PJ (2010) The inflammatory bowel diseases and ambient air pollution: a novel association. Am J Gastroenterol 105:2412–2419CrossRefGoogle Scholar
  15. 15.
    Oikonen M, Laaksonen M, Laippala P, Oksaranta O, Lilius E-M, Lindgren S, Rantio-Lehtimäki A, Anttinen A, Koski K, Erälinna JP (2003) Ambient air quality and occurrence of multiple sclerosis relapse. Neuroepidemiology 22:95–99CrossRefGoogle Scholar
  16. 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. 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
  18. 18.
    Mikuls TR, Payne JB, Deane KD, Thiele GM (2016) Autoimmunity of the lung and oral mucosa in a multisystem inflammatory disease: The spark that lights the fire in rheumatoid arthritis? J Allergy Clin Immunol 137:28–34CrossRefGoogle Scholar
  19. 19.
    Essouma M, Noubiap JJN (2015) Is air pollution a risk factor for rheumatoid arthritis? J Inflamm 12:48CrossRefGoogle Scholar
  20. 20.
    Hart JE, Laden F, Puett RC, Costenbader KH, Karlson EW (2009) Exposure to traffic pollution and increased risk of rheumatoid arthritis. Environ Health Perspect 117:1065–1069CrossRefGoogle Scholar
  21. 21.
    Hart JE, Källberg H, Laden F, Costenbader KH, Yanosky JD, Klareskog L, Alfredsson L, Karlson EW (2013) Ambient air pollution exposures and risk of rheumatoid arthritis. Arthritis Care Res (Hoboken) 65:1190–1196CrossRefGoogle Scholar
  22. 22.
    Hart JE, Källberg H, Laden F, Bellander T, Costenbader KH, Holmqvist M, Klareskog L, Alfredsson L, Karlson EW (2013) Ambient air pollution exposures and risk of rheumatoid arthritis: results from the Swedish EIRA case-control study. Ann Rheum Dis 72:888–894CrossRefGoogle Scholar
  23. 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
  24. 24.
    De Roos AJ, Koehoorn M, Tamburic L, Davies HW, Brauer M (2014) Proximity to traffic, ambient air pollution, and community noise in relation to incident rheumatoid arthritis. Environ Health Perspect 122:1075–1080CrossRefGoogle Scholar
  25. 25.
    Pope CA, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K et al (2002) Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 287:1132–1141CrossRefGoogle Scholar
  26. 26.
    Pope CA, Hansen JC, Kuprov R, Sanders MD, Anderson MN, Eatough DJ (2011) Vascular function and short-term exposure to fine particulate air pollution. J Air Waste Manag Assoc 61:858–863CrossRefGoogle Scholar
  27. 27.
    Salim SY, Kaplan GG, Madsen KL (2014) Air pollution effects on the gut microbiota: a link between exposure and inflammatory disease. Gut Microbes 5:215–219CrossRefGoogle Scholar
  28. 28.
    Zeft AS, Prahalad S, Lefevre S, Clifford B, Mcnally B, Bohnsack JF et al (2009) Paediatric rheumatology Juvenile idiopathic arthritis and exposure to fine particulate air pollution. Clin Exp Rheumatol 27:877–884PubMedGoogle Scholar
  29. 29.
    Wilson WE, Suh HH (1997) Fine particles and coarse particles: concentration relationships relevant to epidemiologic studies. J Air Waste Manag Assoc 47:1238–1249CrossRefGoogle Scholar
  30. 30.
    Pope CA, Dockery DW (2006) Health effects of fine particulate air pollution: lines that connect. J Air Waste Manag Assoc 56:709–742CrossRefGoogle Scholar
  31. 31.
    Glantz SA, Parmley WW (1991) Passive smoking and heart disease. Epidemiology, physiology, and biochemistry. Circulation 83:1–12CrossRefGoogle Scholar
  32. 32.
    Glantz SA, Parmley WW (1995) Passive smoking and heart disease. Mechanisms and risk. JAMA 273:1047–1053CrossRefGoogle Scholar
  33. 33.
    Kish L, Hotte N, Kaplan GG, Vincent R, Tso R, Gänzle M et al (2013) Environmental particulate matter induces murine intestinal inflammatory responses and alters the gut microbiome. PLoS One 8:e62220CrossRefGoogle Scholar

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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