Association of citrullination with the progression of aortic stenosis

• Published in: Scientific reports Vol. 13; no. 1; p. 8919
• Main Authors: Kim, Ah-Ram, Ji, Eunhye, Lee, Sahmin, Hong, Seokchan, Kim, Dae-Hee, Song, Jong-Min, Kang, Duk-Hyun, Song, Jae-Kwan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4019/592; 692/4019/592/75/591; Antibodies; Aortic stenosis; Aortic valve; Citrulline; Degeneration; Echocardiography; Humanities and Social Sciences; Immunohistochemistry; multidisciplinary; Science; Science (multidisciplinary); Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-36153-w

Despite its clinical importance, biomarkers of disease activity in aortic stenosis (AS) are lacking. We investigated the association between anti-cyclic citrullinated peptide (CCP) antibodies and AS. All 678 patients who underwent echocardiography and anti-CCP antibody testing were analysed. Anti-CCP antibody status was categorized as negative, low-positive, and high-positive. In addition, aortic valve (AV) tissues were obtained from the patients with and without AS to analyze the presence of citrullinated proteins. At baseline, 241 (35.5%) subjects with AV degeneration had a higher rate of anti-CCP antibody positivity (42.7% versus 34.6%, p = 0.035) than those without AV degeneration. Out of the 331 (48.8%) subjects who underwent echocardiographic follow-up, progression of AS was observed in 34 (10.3%) patients, with a higher incidence in the high-positive group compared to the low-positive or negative group (19.0% vs. 11.3% vs. 8.4%, respectively; p = 0.041). On multivariable analysis, high anti-CCP antibody positivity was independently associated with progression to AS (odds ratio: 2.312; 95% confidence interval: 1.006–5.310; p = 0.048). Furthermore, immunohistochemistry and Western blotting revealed increased citrullination in diseased AV compared to normal AV tissue. This study demonstrated that a high positive anti-CCP antibody result is associated with AV degeneration and may be an independent factor for AS progression.