Cigarette smoking, disease severity and autoantibody expression in African Americans with recent-onset rheumatoid arthritis

Abstract

Objective-To examine the association of smoking with clinical and serologic features in African Americans with recent-onset rheumatoid arthritis (RA) and to explore whether this association is dependent on the presence of the HLA-DRB1 shared epitope (SE). Methods-InAfrican Americans with recent-onset RA (n = 300), we examined the association of cigarette smoking (current vs. past vs. never and pack-years of exposure) with anti-CCP antibody, rheumatoid factor (RF) (-IgM and -IgA), rheumatoid nodules, and baseline radiographic erosions using logistic and cumulative logistic regression (adjusting for SE status). We also examined for evidence of interaction between smoking status and SE for all outcomes.Results-Although there was no association with RF-IgA seropositivity, current smokers were approximately twice as likely as never smokers to have higher IgA-RF concentrations (based on tertiles; OR = 1.74; 95% CI 1.05-2.88) and nodules (OR = 2.43; 95% CI 1. 13-5.22). These associations were most pronounced in those with more than 20 pack-years of exposure. There was no association of smoking status or cumulative tobacco exposure with anti-CCP antibody, IgM-RF, or radiographic erosions. There was also no evidence of a biologic or statistical SE-smoking interaction for any of the outcomes examined.Conclusion-This is the first study to systematically examine the association of cigarette smoking with RA-related features in African Americans. Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population. The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive license (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licenses to permit this article to be published in Annals of Rheumatic Diseases editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our license http://ard.bmjjournals.com/ifora/license.pdf. Since the first report by Vessey nearly twenty years ago 1 , cigarette smoking has been shown in numerous investigations to be associated with rheumatoid arthritis (RA) susceptibility [2][3][4][5][6][7][8][9][10] . In a national study of disease-discordant monozygotic twins, smoking was associated with a twelve-fold increased risk of RA 11 , an association that appears to be most pronounced in those with long-term exposure (> 20 years duration) 7,12,13 . The impact of smoking on RA risk also appears to be mediated by certain genetic risk factors with the HLA-DRB1 shared epitope (SE) being the most notable. In a recent case-control study, there was no significant association of smoking with seropositive RA in cases without the SE. Ever having smoked, however, was associated with a more than six-fold increased risk of anti-CCP (cyclic citrullinated peptide) antibody-positive RA among those with a s...

Atypical Presentations of Rheumatoid Arthritis

“…This suggests that it is associated with primary pathophysiological mechanisms 15 . In case RA smoking may increase the diseases severity, these associations were most pronounced in those with more than 20 pack-years of exposure Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population 16 .…”

Chronic smoke exposure induces rheumatoid factor and anti‐heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease

“…Another marker used for RA diagnosis is the anti-cyclic citrullinated peptide (CCP) antibody response [9]. Although some epidemiological studies have linked this response to smoking [10,11,14,15], this has not been confirmed in all studies [16].…”

“…Another marker used for RA diagnosis is the anti-cyclic citrullinated peptide (CCP) antibody response [9]. Although some epidemiological studies have linked this response to smoking [10,11,14,15], this has not been confirmed in all studies [16].Heat shock protein-70 (HSP70) encoded in the class III region of major histocompatibility complex (MHC) [17] is a stress response protein induced by heat and smoke exposure [18]. HSP70 is mainly expressed inside cells, but extracellular HSP70 (eHSP70) is found in serum although the physiological role(s) are yet to be established.…”

Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans

“…Scoring was performed using state-of-the-art methods under the auspices of Désirée van der Heijde, a world expert in quantitative assessment of radiographs in rheumatic diseases (34). Furthermore, mTSS scores for participants from CLEAR I and CLEAR II have been validated extensively (35,36). from all three ethnicities using 8,138 genomic annotations (for example, DNAse hypersensitivity, enhancer markings and so on) provided with the PAINTOR3 algorithm; and (4) trimmed these to the top five uncorrelated annotations (correlation coefficient <0.10), excluding the annotations with lower Bayes factors.…”