Murphy, D, Mattey, D and Hutchinson, D (2017) Anti-citrullinated protein antibody positive rheumatoid arthritis is primarily determined by rheumatoid factor titre and the shared epitope rather than smoking per se. PLoS One, 12 (7). e0180655 - ?. ISSN 1932-6203

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OBJECTIVE: To analyse the relationship between rheumatoid factor (RF) titre, smoking and HLA-DRB1 alleles coding a "shared epitope" (SE) in relation to anti-citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA). METHODS: RA patients (n = 658) attending rheumatology clinics in Cornwall, UK (cohort 1) were stratified according to RF and ACPA titre, and smoking pack years at diagnosis. A further 409 RA patients from North Staffordshire, UK (cohort 2) were studied to confirm the relationship between RF levels, smoking and ACPA positivity in relation to SE status. RESULTS: In cohort 1 there was a trend (p<0.01) of increasing ACPA positivity rates with increasing levels of RF without statistically significant differences between patients who had never smoked and smokers (never smoked: 15/71 (21%) RF -ve, vs. 43/64 (67%) RF weak +ve, vs 88/100 (88%) RF strong +ve, ever smoked: 18/70 (26%) RF -ve vs. 66/83 (80%) RF weak +ve vs. 196/210 (93%) RF strong +ve). No significant gender difference was observed. No significant difference between smoking and ACPA positivity was seen in RF negative patients. Smoking >20 pack years conferred an increased risk of anti-CCP positive RA (158/200 (79%)), compared to having never smoked (146/235 (62%), p = <0.01), but this increased risk correlated with smokers' RF positivity as the principal determinant on subsequent regression analysis of cohort 2. In cohort 2, ACPA positivity rates significantly increased with RF positivity and carriage of 1 or 2 SE alleles (p<0.01). Little or no relationship was observed in patients lacking SE. CONCLUSIONS: ACPA positivity in RA strongly associates with increasing RF titre independent of smoking. This relationship is dependent on carriage of SE alleles. There is no relationship between ACPA and smoking in RF negative patients.

Item Type: Article
Uncontrolled Keywords: smoking habits; Rheumatoid Arthritis; Autoantibodies; Regression analysis; Rheumatology; Antibody Response; B cells; Diagnostic medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC925 Diseases of the musculoskeletal system
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 02 Aug 2017 10:36
Last Modified: 02 Aug 2017 10:38

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