Persistence of IgM-RF, anti-CCP2, and ACPA antibodies increases the risk for venous thromboembolic events in patients with rheumatoid arthritis

Although there are ample studies reporting the association between rheumatoid arthritis (RA) and cardiovascular diseases, the pathology underlying the increased venous thromboembolic (VTE) events noted in RA patients has not been completely explored. Now, a recent study published in Rheumatology by a group of Swedish researchers has noted that anti- cyclic citrullinated peptides (CCP2), load of anti-citrullinated protein antibody (ACPA) fine-specificities, and IgM rheumatoid factor (RF) at RA diagnosis are associated with elevated risk for VTE.

The study conducted by Helga and co-workers, involving 2814 newly diagnosed RA patients, examined 213 first-ever VTE events identified through register linkages.  The researchers noted a dose-response association between IgG anti-CCP2 (present in 65% of cohort) and VTE (HR = 1.33, 95%CI 1.00-1.78) in enrolled subjects. In addition, the risk of VTE was found to be proportional to the number of ACPA fine-specificities. A specific association between IgM RF and VTE has also been observed. (HR = 1.38 95%CI 1.04-1.82).

Another Swedish cohort-based study carried out by Molander et al. (2021) have explored the relation between RA disease activity and the risk of VTE. The researchers noted a significant association between the two and the corresponding increase in the risks noted during visits following remission to high disease activity was from 0.52% to 1.08%. The risk ratio for VTE noted upon examining 224 RA patients was 1.88 (95% CI 1.65 to 2.15).

The present study has identified a newer association between routinely evaluated RA-related antibodies and VTE events. Further corroboration of these findings may help in developing effective tool for VTE risk stratification of patients with RA, especially those with a history of VTE or other cardiac risk factors.


  1. Westerlind H, Kastbom A, Rönnelid J, Hansson M, Alfredsson L, Mathsson-Alm L, et al. The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 Oct 18;keac601.
  2. Molander V, Bower H, Frisell T, Askling J. Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden. Annals of the Rheumatic Diseases. 2021 Feb 1;80(2):169–75.