AUTHOR=Robert Marie , Hot Arnaud , Mifsud François , Ndongo-Thiam Ndiémé , Miossec Pierre TITLE=Synergistic Interaction Between High Bioactive IL-17A and Joint Destruction for the Occurrence of Cardiovascular Events in Rheumatoid Arthritis JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01998 DOI=10.3389/fimmu.2020.01998 ISSN=1664-3224 ABSTRACT=

Rheumatoid arthritis (RA) remains a cause of morbidity and mortality in many patients while new treatments have changed the face of the disease. Despite the emergence of these new drugs, cardiovascular (CV) diseases remain more frequent in RA patients compared with the general population. However, predictive biomarkers of RA severity and precise guidelines to manage the CV risk in these patients are still lacking. Pro-inflammatory cytokines contribute both to RA and CV pathogenesis. Focusing on IL-17A, high levels of bioactive IL-17A were associated with destruction in RA but also during myocardial infarction. The study aimed to assess the relationship between bioactive IL-17A, destruction and the occurrence of CV events (CVE) in RA patients with a very long follow-up. Thirty-six RA patients were followed between 1970 and 2012 in Lyon, France. They were tested for bioactive IL-17A and clinical and biological characteristics were recorded at baseline. Then, the occurrence of CVE was registered during the follow-up. To study the bioactive fraction of IL-17A, the bioassay used the ability of human umbilical vein endothelial cells to produce IL-8 in presence of RA plasma samples with or without an anti-IL-17A antibody. Bioactive IL-17A level at baseline was higher in RA patients who later experienced a CVE compared to those without (0.77 vs 0.21 ng/ml, p-value = 0.0095, Mann-Whitney test) and synergized with joint destruction (p-value = 0.020, Kruskal-Wallis test). Through its effects on vessels and thrombosis, high levels of bioactive IL-17A could represent a long-term marker of CV risk.