Increased levels of antibodies to cytokeratin 18 in patients with rheumatoid arthritis and ischaemic heart disease

Abstract

Objective: To determine whether raised levels of antibodies to CK18 in patients with RA are associated with ischaemic heart disease (IHD). Methods: IgA, IgG, and IgM antibodies to CK18 were measured by enzyme linked immunosorbent assay (ELISA) in patients with RA with (n = 34) or without (n = 28) IHD. The relationship between CK18 antibody levels and markers of inflammatory and/or cardiovascular disease was examined. Results: Initial analysis showed that IgG antibody levels to CK18 were higher in patients with RA with IHD than in those without (50.1 v 34.5 AU, p = 0.047), although significance was lost after correction for multiple comparisons. Further analysis showed a significant difference (p = 0.015) between patients with IHD and a positive family history, and patients without IHD and a negative family history (53.7 v 29.0 AU, Kruskal-Wallis multiple comparison Z value test). There was also a significant trend of increasing 10 year cardiovascular risk with increasing CK18 IgG antibody levels (p = 0.01). No association was found between CK18 antibody levels and conventional markers of inflammation or cardiovascular disease, but an association was found between levels of CK18 IgG and IgG antibodies to cytomegalovirus (CMV) (Spearman's r s = 0.379, p corr = 0.04). No evidence for cross reactivity of CK18 antibodies with CMV antigens was found. Conclusion: Levels of IgG antibodies to CK18 are raised in patients with RA with IHD, particularly if they also have a positive family history. This may reflect damage to CK18 containing cells in the cardiac vasculature and/or in atherosclerotic plaques, and may be a useful additional marker for the identification of patients with, or likely to develop, IHD.

Myocardial lipofuscin‐laden lysosomes contain the apoptosis marker caspase‐cleaved cytokeratin‐18

“…We have previously found evidence that acute coronary syndrome (ACS), including unstable angina and acute myocardial infarction are related to increased systemic levels of interleukin-1β-converting enzyme and a caspase-cleaved derivative of the intermediate filament cytokeratin-18 (ccCK-18) [1]. It is furthermore of interest that patients with ACS were reported to produce antibodies against native CK-18 that can be detected as a cytoskeletal component of endothelial cells in cardiac microvasculature [2]. Cleavage of cytokeratins by caspases is an event linked to the decay of cells in apoptosis [3].…”

Prevalence of obesity in rheumatoid arthritis and its association with disease activity and latex positivity in a sample of patients in Erbil

“…4,5 RA is linked with a reduction in life expectancy, 6 mainly due to high risk of developing cardiovascular diseases (CVD) and worst outcomes in individuals affected with RA. 7 Although the exact cause for the CVD in patients with RA is not well understood, but genetic liability , [8][9][10][11] classical CVD risk factors 12,13 as well as the impact of systemic inflammation on the blood vessels 14,15 are all presumed to relate to cardiovascular consequences. 16 RA is also believed to be associated with altered body composition.…”

Serial changes in circulating M30 antigen, a biomarker of apoptosis, in patients with acute coronary syndromes: relationship with the severity of coronary artery disease

“…CK18 has been found to be expressed in endothelial cells of the cardiac microvasculature as well as in vascular smooth muscle cells in the context of atheromatous plaques [7]. Mattey et al [8] have previously reported that levels of IgG antibodies against CK18 are associated with the presence of ischemic heart disease in patients with rheumatoid arthritis, probably as a consequence of the damage to CK18-containing cells.…”

“…Several previous studies have indicated the clinical usefulness of measuring different forms of CK18 in patient sera (M30 antigen for apoptosis and M65 antigen for necrosis) for distinguishing different forms of cell death [6]. Of interest, CK18 has been found to be expressed in endothelial cells and cardiac microvasculature, and patients with ischemic heart disease have been shown to have high titers of serum antibodies against this molecule [7,8]. Interstingly, Adlbrecht et al [9] have recently reported significantly increased M30 levels at the site of coronary occlusion in patients who experienced a myocardial infarction.…”