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Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se : A multicenter cohort study

van Wesemael, Tineke J.; Ajeganova, Sofia; Humphreys, Jennifer; Terao, Chikashi; Muhammad, Ammar; Symmons, Deborah P M; MacGregor, Alex J.; Hafström, Ingiäld; Trouw, Leendert A. LU and van der Helm-van Mil, Annette H M, et al. (2016) In Arthritis Research and Therapy 18(1).
Abstract

Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies. Methods: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals... (More)

Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies. Methods: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals without RA. Furthermore, RA patients fulfilling the 1987 criteria from three early arthritis cohorts from the Netherlands (n = 678), the United Kingdom (n = 761), and Sweden (n = 795) were used. Data on smoking, RF, anti-CCP2, and anti-CarP were available. A total score of autoantibodies was calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by logistic regression. Results: In the population-based non-RA cohort, no association was found between smoking and one autoantibody (RF or anti-CCP2), but smoking was associated with double-autoantibody positivity (OR 2.95, 95% CI 1.32-6.58). In RA patients, there was no association between smoking and the presence of one autoantibody (OR 0.99, 95% CI 0.78-1.26), but smoking was associated with double-autoantibody positivity (OR 1.32, 95% CI 1.04-1.68) and triple-autoantibody positivity (OR 2.05, 95% CI 1.53-2.73). Conclusions: Smoking is associated with the concurrent presence of multiple RA-associated autoantibodies rather than just ACPA. This indicates that smoking is a risk factor for breaking tolerance to multiple autoantigens in RA.

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keywords
Anti-carbamylated protein antibodies, Anti-citrullinated protein antibodies, Rheumatoid arthritis, Rheumatoid factor, Risk factor, Smoking
in
Arthritis Research and Therapy
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:84999828475
  • wos:000390276200007
ISSN
1478-6354
DOI
10.1186/s13075-016-1177-9
language
English
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yes
id
b1e0244e-70b9-4b0f-860a-a3ff4090b1d6
date added to LUP
2016-12-19 07:40:10
date last changed
2017-09-18 11:31:51
@article{b1e0244e-70b9-4b0f-860a-a3ff4090b1d6,
  abstract     = {<p>Background: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies. Methods: A population-based Japanese cohort (n = 9575) was used to investigate the association of smoking with RF and anti-cyclic citrullinated peptide antibodies (anti-CCP2) in individuals without RA. Furthermore, RA patients fulfilling the 1987 criteria from three early arthritis cohorts from the Netherlands (n = 678), the United Kingdom (n = 761), and Sweden (n = 795) were used. Data on smoking, RF, anti-CCP2, and anti-CarP were available. A total score of autoantibodies was calculated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by logistic regression. Results: In the population-based non-RA cohort, no association was found between smoking and one autoantibody (RF or anti-CCP2), but smoking was associated with double-autoantibody positivity (OR 2.95, 95% CI 1.32-6.58). In RA patients, there was no association between smoking and the presence of one autoantibody (OR 0.99, 95% CI 0.78-1.26), but smoking was associated with double-autoantibody positivity (OR 1.32, 95% CI 1.04-1.68) and triple-autoantibody positivity (OR 2.05, 95% CI 1.53-2.73). Conclusions: Smoking is associated with the concurrent presence of multiple RA-associated autoantibodies rather than just ACPA. This indicates that smoking is a risk factor for breaking tolerance to multiple autoantigens in RA.</p>},
  articleno    = {285},
  author       = {van Wesemael, Tineke J. and Ajeganova, Sofia and Humphreys, Jennifer and Terao, Chikashi and Muhammad, Ammar and Symmons, Deborah P M and MacGregor, Alex J. and Hafström, Ingiäld and Trouw, Leendert A. and van der Helm-van Mil, Annette H M and Huizinga, Tom W J and Mimori, Tsuneyo and Toes, René E M and Matsuda, Fumihiko and Svensson, Björn and Verstappen, Suzanne M M and van der Woude, Diane},
  issn         = {1478-6354},
  keyword      = {Anti-carbamylated protein antibodies,Anti-citrullinated protein antibodies,Rheumatoid arthritis,Rheumatoid factor,Risk factor,Smoking},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Smoking is associated with the concurrent presence of multiple autoantibodies in rheumatoid arthritis rather than with anti-citrullinated protein antibodies per se : A multicenter cohort study},
  url          = {http://dx.doi.org/10.1186/s13075-016-1177-9},
  volume       = {18},
  year         = {2016},
}