medwire news: Studies have shown that the risk of venous thromboembolism (VTE) is highly associated with the presence of autoantibodies associated with rheumatoid arthritis (RA).
Immunoglobulin (Ig) G against second-generation cyclic citrullinated peptides (anti-CPP2), fine-specificity spread of 20 anti-citrullinated protein antibodies (ACPA), and IgM anti-rheumatoid factor (RF) have previously been associated with risk.Myocardial infarction, stroke, and cardiovascular death, researchers explain Rheumatology.
To determine the impact of these autoantibodies on VTE risk in patients with RA, Helga Westerlind (Karolinska Institutet, Stockholm, Sweden) and coworkers enrolled with new diagnoses of RA during 1996. We collated information from 2782 participants in the EIRA study. and in 2009, there was no history of VTE.
With a median follow-up of 15.5 years, 213 experienced their first VTE event, for a rate of 5.0 events per 1,000 person-years.
Overall, 64.6% of patients were positive for IgG anti-CCP2 and 46.5% were positive for IgA anti-CCP2, and these individuals were more likely than their negative counterparts to experience VTE (hazard ratio [HR]=1.33 and 1.35, respectively).
Furthermore, the risk of IgG anti-CCP2-positive VTE showed a dose-response relationship, suggesting that individuals with low (25 to <75 AU/mL) and extreme (≥1500 AU/mL) levels, compared with negative individuals was 1.41. and 1.49 times more likely to experience VTE, respectively.
The team identified 18 ACPA fine-specificities that occurred in more than 10% of the cohort, with a median of 6 per patient.
The risk of VTE increased with the number of identified ACPA fine specificities, with HRs of 1–4, 5–10, and 11–17, and those without ACPA fine specificity of 1.39, 1.68, and 1.56, respectively. did.
Two fine specificities, hnRNP-derived Cit-Peptide-Z1 (HR=1.40) and Cit-Peptide-1 (HR=1.47), were independently associated with increased risk of VTE.
However, Westerlind et al. noted that none of the six autoantibodies to citrullinated fibrinogen were significantly associated with VTE risk.
Although three RF isotypes have been identified, only IgM RF is significantly associated with VTE risk, with an HR of 1.39, they say.
Information was available on shared epitopes on smoking habits and HLA-DRB1 alleles in 2714 patients, but adjustment for these confounders had “little impact” on the relationship between autoantibody positivity and VTE risk. No,” Westerlind and co-authors observe.
Overall, the researchers say their findings are “in line with other studies.” [cardiovascular] Note, however, that “the mechanisms underlying this association remain unclear.”
And because of the lack of longitudinal information on RA disease activity, they argued that “the association between RA-associated autoantibodies and VTE risk was mediated by or independent of accumulated RA disease activity.” We acknowledge that this means that this study was unable to determine whether
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Rheumatology 2022; doi:10.1093/rheumatology/keac601
