In Rheumatoid Arthritis, Smoking Is Not Associated with Anti-Citrullinated Protein Antibodies per Se, but with the Concurrent Presence of Rheumatoid Factor, Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies

Tineke van Wesemael¹, Ammar Muhammad¹, Sofia ajeganova^2,3, Jennifer Humphreys⁴, Deborah P.M. Symmons^5,6, Alex J Macgregor⁷, Ingiäld Hafström², Leendert Trouw¹, T. W. J. Huizinga¹, Björn Svensson⁸, René E. M. Toes¹, Suzanne M. Verstappen⁹ and Diane van der Woude¹, ¹Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ²Rheumatology, Department of Medicine Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden, ³Rheumatology, Leiden University Medical Center, LEIDEN, Netherlands, ⁴Manchester Academic Health Science Centre, Arthritis Research UK Epidemiology Unit,, Manchester, United Kingdom, ⁵Centre for Musculoskeletal Research, University of Manchester, Arthritis Research UK Centre for Epidemiology, Manchester, United Kingdom, ⁶NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom, ⁷Rheumatology, Norfolk and Norwich University Hospital, Norwich, United Kingdom, ⁸Section of Rheumatology, Department of Clinical Sciences,, University of Lund, Lund, Sweden, ⁹Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: autoantibodies, pathogenesis and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis I

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose :
In rheumatoid arthritis (RA) a biological hypothesis has been proposed linking
smoking with citrullination, the development of anti-citrulline autoimmunity
and anti-citrullinated protein antibodies (ACPA) and subsequently RA¹.
The fact that smoking is associated with several autoantibodies in other
autoimmune diseases raised the question if in RA smoking is solely associated
with ACPA or with autoantibodies in general.

Objectives:
To
investigate if in patients with RA, smoking is specifically associated with ACPA
or with the presence of other autoantibodies as well.

Methods :
Patients from three independent early
arthritis cohorts were used: the Leiden Early Arthritis Clinic (n=767), the British
Norfolk Arthritis Register (n=761) and the Swedish Better
Anti‐Rheumatic
Fharmaco Therapy cohort (n=795). All patients fulfilled the 1987 RA criteria
and had symptom duration of less than two years. Smoking (ever versus never)
and autoantibody status: rheumatoid factor (RF), ACPA and anti-carbamylated
protein antibodies (anti-CarP), were determined at inclusion into this studies.
A meta-analysis was performed calculating odds ratios and 95% confidence
intervals to assess the association between
number of autoantibodies and smoking, using 2×2 comparison with seronegative
RA patients as reference category. In the Leiden EAC, interaction between
smoking and shared epitope (SE) was assessed using the three measures of
biological interaction: relative excess risk due to interaction,
the attributable proportion due to interaction and
the synergy index.

Results: There
was no significant association between smoking and seropositive RA in patients
who were positive for one autoantibody only (n=406). However, smoking was
significantly associated with double (n=429) and triple autoantibody-positivity
(n= 606) (figure 1). Furthermore, interaction measures
between smoking and SE were not significant for patients with one autoantibody,
partly significant for patients with two autoantibodies, whereas all three
measures were significant in the triple-positive group (table 1).

Conclusion:
Smoking and the interaction between smoking and SE is not solely associated
with ACPA-positive RA, but with the concurrent presence of all three RA-associated
autoantibodies. These data indicate that current
hypotheses on the role of smoking in the pathophysiology of RA may need to be refined by taking the presence of other
auto-antibodies into account.

References

1.
Klareskog et al. 2006 Arthritis Rheum. 54:38

Disclosure: T. van Wesemael, None; A. Muhammad, None; S. ajeganova, None; J. Humphreys, None; D. P. M. Symmons, None; A. J. Macgregor, None; I. Hafström, None; L. Trouw, None; T. W. J. Huizinga, None; B. Svensson, None; R. E. M. Toes, None; S. M. Verstappen, None; D. van der Woude, None.

To cite this abstract in AMA style:

van Wesemael T, Muhammad A, ajeganova S, Humphreys J, Symmons DPM, Macgregor AJ, Hafström I, Trouw L, Huizinga TWJ, Svensson B, Toes REM, Verstappen SM, van der Woude D. In Rheumatoid Arthritis, Smoking Is Not Associated with Anti-Citrullinated Protein Antibodies per Se, but with the Concurrent Presence of Rheumatoid Factor, Anti-Citrullinated Protein Antibodies and Anti-Carbamylated Protein Antibodies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/in-rheumatoid-arthritis-smoking-is-not-associated-with-anti-citrullinated-protein-antibodies-per-se-but-with-the-concurrent-presence-of-rheumatoid-factor-anti-citrullinated-protein-antibodies-and-a/. Accessed .

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