Increased levels of antibodies to CK18 in patients with RA and ischaemic heart disease

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Ann Rheum Dis. 2004 Apr;63(4):420-425.

Increased levels of antibodies to cytokeratin 18 in patients with

rheumatoid arthritis and ischaemic heart disease.

Mattey DL, Dawes PT, Nixon NB, Goh L, Banks MJ, Kitas GD.

Staffordshire Rheumatology Centre, The Haywood, High Lane, Burslem,

Stoke-on-Trent, Staffordshire ST6 7AG, UK. Department of Rheumatology,

Dudley Group of Hospitals NHS Trust and Department of Rheumatology,

Division of Immunity and Infection, University of Birmingham, UK.

Department of Cardiology, Dudley Group of Hospitals NHS Trust,

Birmingham, UK.

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.

PMID: 15020337

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