Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis

Król, Aleksandra; Garred, Peter; Heegaard, Nhh; Christensen, Anders Lyhne; Hetland, Merete Lund; Stengaard‐Pedersen, Kristian; Junker, Peter; Madsen, H. O.; Lottenburger, Tine; Ellingsen, Torkell; Andersen, Lars Peter Holst; Hansen, I.; Pedersen, J. K.; Svendsen, Anders Jørgen; Tarp, Ulrik; Pødenphant, Jan; Lindegaard, Hanne; Østergaard, Mikkel; Hørslev‐Petersen, Kim; Jacobsen, Søren

doi:10.3109/03009742.2014.918651

Cited by 22 publications

(20 citation statements)

References 12 publications

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“…36 In a recent study of treatment-naïve adults with early RA, RF IgM, RF IgA and anti-CCP positivity were associated with erosive disease among ever smokers but not among never smokers. 38 In our communitybased cohort, we found that smoking modified the associations of RF IgM and anti-CCP-but not RF IgA-with HAA and ILA. Our data suggest that RF IgA might lead to lung injury, inflammation and fibrosis in a smoking-independent fashion, while RF IgM and anti-CCP might require concomitant or prior cigarette smoking before ILD pathology develops.…”

Section: Discussionmentioning

confidence: 62%

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

Bernstein

Barr

Austin

et al. 2016

Thorax

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Background Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults. Methods We measured serum rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAA; CT attenuation values between −600 and −250 HU) on cardiac CT in 6,736 community-dwelling U.S. adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured interstitial lung abnormalities (ILA) in 2,907 full-lung CTs at 9.5-year median follow-up. We used generalized linear and additive models to examine associations between autoantibodies and both HAA and ILA, and tested for effect modification by smoking. Results In adjusted models, HAA increased by 0.49% (95% CI 0.11–0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50–1.40%) per RF IgA doubling. ILA prevalence increased by 11% (95% CI 3–20%) per RF IgA doubling. Smoking modified the associations of both RF IgM and anti-CCP with both HAA and ILA (interaction p-values varied from 0.01 to 0.09). Among ever smokers, HAA increased by 0.81% (95% CI 0.33–1.30%) and ILA prevalence increased by 14% (95% CI 5–24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45–2.18%) and ILA prevalence increased by 13% (95% CI 2–24%) per anti-CCP doubling. Among never smokers, no meaningful associations were detected. Conclusions RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.

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Section: Discussionmentioning

confidence: 62%

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

Bernstein

Barr

Austin

et al. 2016

Thorax

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“…In genetically predisposed individuals, protein citrullination poses the potential risk of production of anticitrullinated peptide/protein antibodies (ACPA), which are strongly associated with development of RA [31,32]. In this context, the combination of current smoking and possession of HLA-DRB1 shared epitope (SE) alleles, both of which are independently associated with RA, is closely associated with the appearance of ACPA, an event which precedes, and is predictive of, the development of RA [33][34][35][36][37][38]. The specificity of ACPA for their target citrullinated proteins appears to increase closer to disease onset and progression [37].…”

Section: Smoking and Ramentioning

confidence: 99%

“…In this context, the combination of current smoking and possession of HLA-DRB1 shared epitope (SE) alleles, both of which are independently associated with RA, is closely associated with the appearance of ACPA, an event which precedes, and is predictive of, the development of RA [33][34][35][36][37][38]. The specificity of ACPA for their target citrullinated proteins appears to increase closer to disease onset and progression [37]. In the case of patients with early-onset RA, previous smoking is associated with a dose-dependent occurrence of ACPA in both the lungs and circulation [35,39].…”

Section: Smoking and Ramentioning

confidence: 99%

Smoking and Air Pollution as Pro-Inflammatory Triggers for the Development of Rheumatoid Arthritis

Anderson

Meyer

Ally

et al. 2016

NICTOB

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Smoking is now well recognised not only as a risk factor for rheumatoid arthritis (RA), but also as a determinant of disease activity, severity, response to therapy, and possibly mortality. Recent studies have provided significant insights into the molecular and cellular mechanisms which underpin the pathogenesis of smokingrelated RA. These involve release of the enzymes, peptidylarginine deiminases (PADs) 2 and 4 from smoke-activated, resident and infiltrating pulmonary phagocytes. PADs, in turn, mediate the conversion of various endogenous proteins to putative citrullinated autoantigens. In genetically susceptible individuals, these autoantigens trigger the production of anti-citrullinated peptide/protein pathogenic autoantibodies (ACPA), an event which precedes the development of RA. This review is focused primarily on smoking-mediated harmful chronic inflammatory responses, both local and systemic, which promote the formation of ACPA, as well as the possible involvement of other types of outdoor and indoor pollution in the pathogenesis of RA. This is preceded by a brief overview of the evidence implicating smoking as a risk factor for development of ACPA-positive RA.Keywords: Anti-citrullinated peptide/protein antibodies; airway microbiota; atmospheric pollution; heavy metals; peptidylarginine deiminases; smoking cessation strategies. ImplicationsChronic inflammatory mechanisms operative in the lungs of smokers lead to the production of anti-citrullinated protein antibodies which, in turn, drive the development of rheumatoid arthritis. These mechanistic insights not only reinforce the association between smoking and risk for rheumatoid arthritis, but also the necessity to increase the level of awareness in those at highest risk.

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“…[3][4][5][6] Autoimmune antibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) have prognostic significance for the development of RA. 7 Relationship between smoking and production of RF and anti-CCP has been reported. 8 RF positivity is found in 70-80% of patients with RA 9 and frequency of RF positivity was shown to be higher in smokers in the general population and long-term smokers among patients with RA.…”

mentioning

confidence: 99%

“…12 There are studies with conflicting results that determined a relationship between smoking and disease activity, radiologic progression and response to treatment. 4,7,8,13 In our knowledge, no study has been conducted with Turkish RA patients investigating the relationship between smoking and joint damage, disease activity and disability. Therefore, in this study, we aimed to investigate the relationship between smoking and structural damage, autoimmune antibodies, and disability in RA patients.…”

mentioning

confidence: 99%

Relationship Between Smoking and Structural Damage, Autoimmune Antibodies, and Disability in Rheumatoid Arthritis Patients

Sivas

2018

Arch Rheumatol

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Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis

Cited by 22 publications

References 12 publications

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis

Smoking and Air Pollution as Pro-Inflammatory Triggers for the Development of Rheumatoid Arthritis

Relationship Between Smoking and Structural Damage, Autoimmune Antibodies, and Disability in Rheumatoid Arthritis Patients

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