Association of anti-citrullinated protein or peptide antibodies with left ventricular structure and function in rheumatoid arthritis

Abstract

Objective. High levels of ACPAs in RA are associated with more severe arthritis and worse prognosis. However, the role of ACPAs in mediating the increased risk of heart failure in RA remains undefined. We examined whether specific ACPAs were associated with subclinical left ventricular (LV) phenotypes that presage heart failure.Methods. Sera from RA patients without clinical cardiovascular disease were assayed for specific ACPAs using a custom Bio-Plex bead assay, and their cross-sectional associations with cardiac magnetic resonance-derived LV measures were evaluated. High ACPA level was defined as 5 75th percentile. Findings were assessed in a second independent RA cohort with an expanded panel of ACPAs and LV measures assessed by 3D-echocardiography.Results. In cohort 1 (n = 76), higher levels of anti-citrullinated fibrinogen 41 60 and anti-citrullinated vimentin antibodies were associated with a 10 and 6% higher adjusted mean LV mass index (LVMI), respectively, compared with lower antibody levels (P < 0.05). In contrast, higher levels of anticitrullinated biglycan 247 266 were associated with a 13% lower adjusted mean LVMI compared with lower levels (P < 0.001). In cohort 2 (n = 74), the association between ACPAs targeting citrullinated fibrinogen and citrullinated vimentin peptides or protein and LVMI was confirmed: higher anticitrullinated fibrinogen 556 575 and anti-citrullinated vimentin 58 77 antibody levels were associated with a higher adjusted mean LVMI (19 and 15%, respectively; P < 0.05), but no association with biglycan was found.Conclusion. Higher levels of antibodies targeting citrullinated fibrinogen and vimentin peptides or protein were associated with a higher mean LVMI in both RA cohorts, potentially implicating autoimmune targeting of citrullinated proteins in myocardial remodelling in RA.Key words: anti-citrullinated peptide antibody (ACPA), RA, ventricular mass, CVD Rheumatology key messages. Higher levels of ACPAs targeting citrullinated fibrinogen and citrullinated vimentin peptides or protein were associated with higher left ventricular mass index. . Seroreactivity towards citrullinated proteins may play a role in myocardial remodelling in RA.

Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

“…For instance, higher circulating concentrations of anti-cit-fibrinogen and anti-cit-vimentin antibody were associated with increased left ventricular mass in independent rheumatoid arthritis cohorts free of cardiovascular disease 59. This was not observed for antibodies recognizing non-citrullinated (native) peptides/proteins.…”

Roles of Oral Infections in the Pathomechanism of Atherosclerosis

“…In line with this hypothesis, periodontitis was independently associated with rheumatoid arthritis in multiple epidemiological studies (reviewed in ref. [ 64 ]) and a specific set of anti-citrullinated peptide antibodies (ACPA), which was present in rheumatoid arthritis patients, was associated with coronary artery calcification, a well established surrogate marker of coronary atherosclerosis [ 65 ].…”

Potential Impact of Oral Inflammations on Cardiac Functions and Atrial Fibrillation

“…Hypercitrullination of proteins in cardiomyocytes of the failing heart is likely important, because rheumatoid arthritis is strongly associated with AF [ 66 ]. Anticitrullinated protein antibodies were significantly associated with altered left ventricular structure and function in a recent study on patients with rheumatoid arthritis [ 110 ], and citrullinated proteins with impaired function could be identified in human myocardial samples from healthy and heart failure patients [ 111 ]. However, specific effects that support an ability of LtxA to trigger AF via citrullination or other mechanisms have not been reported.…”