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. 2002 Feb;61(2):110–114. doi: 10.1136/ard.61.2.110

High titres of serum antinuclear antibodies, mostly directed against nucleolar antigens, are associated with the presence of coronary atherosclerosis

D Grainger 1, H Bethell 1
PMCID: PMC1753986  PMID: 11796395

Abstract

Background: Inappropriate inflammation is a key mechanism in the development of atherosclerosis. Antibodies against components of the atherosclerotic lesion, in particular, oxidised low density lipoprotein, have been described.

Objective: To determine whether a systemic autoimmune response, characterised by the presence of high titres of antinuclear antibodies, is associated with the presence of coronary atherosclerosis.

Methods: Serum was prepared from 40 subjects (aged 53–76) with at least 50% stenoses of three main coronary arteries (TVD subjects), and 30 subjects (aged 48–74) with no evidence of coronary atherosclerosis (NCA subjects) determined by coronary angiography.

Results: Antinuclear antibodies (ANA), characterised by immunofluorescent detection of human antibodies bound to HEp-2000 cells, were detected at a titre of at least 1/40 in 28 (70%) of the TVD subjects, but only five (17%) of the NCA patients (odds ratio 11.67 (95% confidence interval (CI) 3.91 to 17.82; p<0.001)). Most ANA positive TVD subjects had a pattern typical of antibodies directed against nucleolar antigens. The antigen has not yet been identified, but several common extractable antigens were excluded. The presence of ANA was not associated with incidence of prior myocardial infarction among the TVD group.

Conclusion: The presence of ANA, commonly associated with autoimmune diseases, is substantially more prevalent among subjects with severe coronary atherosclerosis than those with normal coronary arteries. This association merits further assessment as a potentially useful indicator of increased risk of coronary heart disease.

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Figure 1 .

Figure 1

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Immunofluorescent detection of ANA binding to HEp-2000 cells. In each case the serum was from a subject in the TVD group and was assayed at a dilution of 1/40 in accordance with the manufacturer's instructions. Bar=5 µm. (A) Cells stained with serum containing no detectable ANA. (B) Cells stained with serum containing ANA that give an atypical speckled pattern, characteristic of detection of nucleolar antigens. (C) Cells stained with serum containing ANA that react with DNA (later confirmed using Crithidia luciliae). Intense staining of the metaphase chromosomes is indicated by the arrow. (D) Cells stained with serum containing ANA that yield a typical speckled pattern, possibly owing to reaction with nuclear matrix components.

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