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Abstract Number: 348

Smoking Status Is Associated with Inflammatory Cytokine Profile and Disease Activity: Decreased Inflammation and Disease Improvement with Smoking Cessation?

Jeremy Sokolove1, Harlan Sayles2, Catriona Wagner3, Lauren J. Lahey1, Geoffrey M. Thiele4, William H. Robinson1, Andreas Reimold5, Gail S. Kerr6, Grant W. Cannon7 and Ted R. Mikuls2, 1VA Palo Alto Healthcare System and Stanford University, Palo Alto, CA, 2Omaha VA Medical Center and University of Nebraska Medical Center, Omaha, NE, 3VA Palo Alto Heatlh Care System and Stanford University, Palo Alto, CA, 4Internal Medicine, Omaha VA Medical Center and University of Nebraska Medical Center, Omaha, NE, 5Rheumatology, Dallas VA and Univ of TX Southwestern Med Ct, Dallas, TX, 6Rheumatology, Washington DC VAMC, Georgetown and Howard University, Washington, DC, 7Division of Rheumatology, Salt Lake City VA and University of Utah, Salt Lake City, UT

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ACPA, cytokines, Disease Activity, environmental factors and rheumatoid arthritis (RA)

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Session Information

Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity

Session Type: Abstract Submissions (ACR)

Background/Purpose: Cigarette smoking is a risk factor for RA and has been associated with increased disease severity and lower rates of disease remission.  We examined whether smoking cessation might be associated with reduced disease activity and investigated the association of autoantibody levels with smoking status.

Methods:   RA patients from the Veterans Affairs RA (VARA) registry were studied (n = 1468, 76.9% anti-CCP2+, 90.7% male, median age 63 [IQR 57-72], median disease duration 8.45 years [IQR 2.8-18]).  Baseline serum samples were evaluated for levels of 19 distinct ACPA and 17 cytokines using the BioPlex platform.  Baseline smoking status was recorded as current, former, or never.  Cross-sectional associations of baseline smoking status with disease activity (DAS28) and its constituents as well as baseline levels of ACPA, and baseline levels of cytokines were assessed.

Results:   Multiple measures of RA disease activity including DAS28 were significantly higher among current smokers compared with either former or never smokers (P<0.01), an effect limited to the seropositive (anti-CCP2 positive) population (Table 1).  The number of inflammatory cytokines found in high concentration was significantly higher among current smokers compared with both former and non-smokers (FDR q-value <0.1%).  Levels of both anti-CCP2 as well as ACPA subtypes were lower in never smokers but similar between current and former smokers while levels of RF were highest in current smokers, and lower in both former smokers and lowest in never smokers (Table 2).

Conclusion:   Current smoking is strongly associated with increased RA disease activity as well as elevation in pro-inflammatory serum cytokines compared to both former and never smokers.  Our findings suggest that continued tobacco exposure promotes greater RA disease activity, particularly in ACPA positive patients though independent of titer or specificity.  The observation of reduced disease activity among former smokers, approaching that of never smokers, suggests that the effects of smoking may be reversed by smoking cessation.  Whether RF may be a mediator of this effect remains to be clarified.

DAS28

Log(CRP)

ACPA  #Pos

ACPA Score

Cytokine #Pos

Cytokine score

CCP2 level

RF level

Current smoker

4.6

1.9

2.7

24.3

1.8

22.9

395.9

593.1

Former smoker

3.9

1.7

2.6

23.2

1.1

18.9

360.9

350.5

Never smoker

3.7

1.7

2.1

19.7

1.1

14.6

278.1

239.0

P-values*

Global ANOVA

< 0.001

0.044

0.043

0.019

0.001

0.085

0.020

<0.001

Current vs. Never

< 0.001

NS

NS

< 0.05

< 0.01

NS

<0.05

<0.001

Current vs. Former

< 0.001

NS

NS

NS

< 0.01

NS

NS

<0.001

Former vs. Never

NS

NS

NS

NS

NS

NS

NS

NS

Table 1:  Measures of disease activity, ACPA, and cytokine expression among anti-CCP2 positive RA patients; *p-values among smoking groups generated using Scheffe’s method for multiple comparisons


Disclosure:

J. Sokolove,
None;

H. Sayles,
None;

C. Wagner,
None;

L. J. Lahey,
None;

G. M. Thiele,
None;

W. H. Robinson,
None;

A. Reimold,
None;

G. S. Kerr,
None;

G. W. Cannon,

AbbVie,

2;

T. R. Mikuls,

Genetech/Roche,

2.

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