Smoking as a risk factor for rheumatoid arthritis: predominant association with IgA autoantibodies – comprehensive analysis of anti-modified protein antibodies with smoking and genetic risk factors in rheumatoid arthritis
Authors' conclusion
These data provide a pivotal refinement of existing knowledge regarding risk factor associations for RA and lend novel support to the hypothesis that smoking may exert its effect on RA by the induction of local (auto)immune responses at mucosal sites.
Study context
- Population
- Rheumatoid arthritis (RA) patients with ACPA, AAPA and RF isotypes (IgA, IgG, IgM) measured by ELISAreplication meta-analysis n = 3309
- Participants
- 618 patients
- Exposure
- Smoking vs no smoking, by AMPA isotype
- Outcome
- Association between smoking, genetic risk factors for RA and presence of specific AMPA isotypes, particularly IgA
Methodological detailslogistic regression, replication meta-analysis
- Logistic regression
- Replication meta-analysis
Main finding
As reported in the abstract
Association of smoking with IgA AMPA, corrected for concurrent AMPA IgG
Smoking and ACPA-IgA, OR [interval as printed]
OR 1.89
1.14–3.12
Smoking and AAPA-IgA, OR [interval as printed]
2.30
1.35–3.94
Observational data: associations, not effects.
Further findings
Replication meta-analysis (3309 RA patients): smoking and ACPA isotype combination
- ACPA-IgA plus ACPA-IgG, OR
- 2.05 [1.69-2.49], p < 0.001
- ACPA-IgG only, OR
- 1.18 [0.97-1.44], p = 0.11
Gene-environment interaction (HLA shared epitope × smoking)
- Only seen in patients both ACPA-IgG and ACPA-IgA positive, not in those only ACPA-IgG positive
Original publication
Smoking as a risk factor for rheumatoid arthritis: predominant association with IgA autoantibodies – comprehensive analysis of anti-modified protein antibodies with smoking and genetic risk factors in rheumatoid arthritis. Arthritis Res Ther. Published 8 May 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →