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. 2016 Nov;55(11):1969-1977.
doi: 10.1093/rheumatology/kew285. Epub 2016 Jul 31.

Increased inflammation and disease activity among current cigarette smokers with rheumatoid arthritis: a cross-sectional analysis of US veterans

Jeremy Sokolove  1   2 , Catriona A Wagner  3   2 , Lauren J Lahey  3   2 , Harlan Sayles  4   5 , Michael J Duryee  4   5 , Andreas M Reimold  6   7 , Gail Kerr  8   9   10 , William H Robinson  3   2 , Grant W Cannon  11   12 , Geoffrey M Thiele  4   5 , Ted R Mikuls  4   5
Affiliations

Increased inflammation and disease activity among current cigarette smokers with rheumatoid arthritis: a cross-sectional analysis of US veterans

Jeremy Sokolove et al. Rheumatology (Oxford). 2016 Nov.

Abstract

Objectives: Cigarette smoking is a major risk factor for RA and has been associated with increased disease severity and lower rates of disease remission. We hypothesized that inflammation and disease activity would be associated with smoking status and this would be related to levels of ACPA.

Methods: RA patients from the Veterans Affairs RA registry were studied (n = 1466): 76.9% anti-CCP2 positive, 89% male, median age 63 years (interquartile range 57-72), median disease duration 8.45 years (interquartile range 2.8-18). Baseline serum samples were evaluated for levels of anti-CCP2, RF, 19 distinct ACPAs and 17 cytokines. Smoking status at baseline was recorded as current, former or never. The association of smoking status with cytokines, autoantibodies and disease activity (DAS28) was evaluated.

Results: Among anti-CCP-positive RA patients, RA-associated cytokines (false-discovery rates q < 0.1%) and DAS28 (P < 0.01) were higher in current smokers compared with former or never smokers. DAS28 and cytokine levels were similar between former and never smokers. In contrast, ACPA concentrations were higher among both current and former smokers compared with never smokers, and levels of ACPA were not associated with DAS28 or cytokine levels.

Conclusion: Among anti-CCP2-positive RA patients, current smoking status is associated with elevations in pro-inflammatory cytokines and increased RA disease activity. Similar levels of inflammation and disease activity among former and never smokers suggests that the detrimental effects of smoking could be ameliorated through tobacco cessation. The effect of tobacco cessation on RA disease activity should be evaluated prospectively.

Keywords: disease activity; inflammation; rheumatoid arthritis; smoking.

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Figures

<sc>Fig</sc>. 1
Fig. 1
Differential associations of serum cytokines, ACPAs and RF with smoking status Anti-CCP2-positive patients were categorized into subgroups including current (n = 321), former (n = 599) or never (n = 210) smokers. Levels of serum cytokines were measured by multiplex immunoassay, levels of ACPA were assessed by measurement of autoantibodies against 37 putative targets of the RA immune response, and levels of IgM RF were measured by nephelometry. Comparisons between groups were performed using the Kruskal–Wallis test with Tukey’s multiple comparison post hoc test. The cytokine score (A) and number of cytokines (B) were higher among current smokers, whereas levels of anti-CCP2 (C), ACPA score (E) and ACPA number (F) were higher in both current and former smokers compared with never smokers. (D) RF titre was significantly higher among current smokers than former and never smokers.
<sc>Fig</sc>. 2
Fig. 2
Increased RA-associated cytokines are identified among current compared with former and never smokers Levels of 17 cytokines were compared between age- and sex-matched subgroups of current, former and never smokers (n = 107 subjects per group) using a bead-based multiplex cytokine assay. Using significance analysis of microarrays, output was sorted based on false-discovery rates in order to identify cytokines with the greatest differences between subgroups.
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