Abstract | OBJECTIVE: METHODS: Two cohorts of patients with early RA, from the first Epidemiological Investigations of RA trial (n = 1,663) and the second Early Intervention in RA trial (n = 199), were grouped into 4 subsets based on anti-CCP subclass status ( IgG-/ IgA-, IgG-/ IgA+, IgG+/ IgA-, and IgG+/ IgA+), and each subset was compared with regard to associations with smoking (current and former) and presence of SE. Interaction between smoking and SE was calculated using the attributable proportion (AP) due to interaction (assessing deviation from additivity of effects). RESULTS: Smoking was overrepresented among IgA anti-CCP-positive RA patients, regardless of whether IgG anti-CCP were present, whereas in patients with IgG anti-CCP alone, no association with smoking was found. SE alleles were overrepresented among IgG anti-CCP-positive patients, regardless of IgA anti-CCP status, and was not seen in patients with IgA anti-CCP alone. An interaction between ever smoking and SE was found with regard to the risk of IgG+/IgA+ RA (AP 0.5, 95% confidence interval 0.4, 0.6). No significant interaction was observed with regard to the risk of IgG-/IgA+ RA or IgG+/ IgA- RA. CONCLUSION: In patients with RA, a history of ever smoking was associated with seropositivity for IgA anti-CCP antibodies, whereas presence of SE was associated with seropositivity for IgG anti-CCP antibodies. An interaction between ever smoking and the SE was limited to the RA subset characterized by seropositivity for both IgG and IgA anti-CCP. These findings provide novel evidence that anti-CCP-positive RA can be divided into at least 3 serologically distinct subsets associated with different risk factors, indicating different modes of pathogenesis in RA.
|
Authors | Anna Svärd, Thomas Skogh, Lars Alfredsson, Anna Ilar, Lars Klareskog, Camilla Bengtsson, Alf Kastbom |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 67
Issue 8
Pg. 2032-7
(May 2015)
ISSN: 2326-5205 [Electronic] United States |
PMID | 25916813
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2015, American College of Rheumatology. |
Chemical References |
- Autoantibodies
- Epitopes
- HLA-DRB1 Chains
- Immunoglobulin A
- Immunoglobulin G
- Peptides, Cyclic
- cyclic citrullinated peptide
|
Topics |
- Arthritis, Rheumatoid
(genetics, immunology)
- Autoantibodies
(immunology)
- Cohort Studies
- Epitopes
(immunology)
- Female
- Genotype
- HLA-DRB1 Chains
(genetics)
- Humans
- Immunoglobulin A
(immunology)
- Immunoglobulin G
(immunology)
- Male
- Middle Aged
- Peptides, Cyclic
(immunology)
- Smoking
(genetics, immunology)
|