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Rheumatology 2002; 41: 869-875
© 2002 British Society for Rheumatology

Original Papers

Elevated expression of the genes encoding TNF-{alpha} and thromboxane synthase in leucocytes from patients with systemic sclerosis

V. Young1,*, M. Ho2, H. Vosper1, J. J. F. Belch2 and C. N. A. Palmer1,

1 Biomedical Research Centre and
2 Section of Vascular Medicine and Biology, Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK

Objective. To determine the expression of molecular markers of prostanoid/fatty acid signalling in leucocytes of patients with systemic sclerosis (SSc).

Methods. Gene expression in patient leucocytes was analysed using real-time fluorescence reverse transcriptase polymerase chain reaction for tumour necrosis factor {alpha} (TNF-{alpha}), thromboxane synthase (TXAS, CYP5A), prostacyclin synthase (CYP8A), monocyte chemoattractant protein-1 (MCP-1), peroxisome proliferator-activated receptors (PPAR) {alpha}, {delta} and {gamma}, low-density lipoprotein-associated lipoprotein lipase A2 (LDL-PLA2), apolipoprotein E (apoE) and cholesterol 27-hydroxylase (CYP27).

Results. Both TNF-{alpha} and TXAS showed an increase in mean expression in the diseased group (6.3-fold and 5.6-fold respectively, P<0.0001). These two markers, along with CYP27, PPAR{gamma} and apoE, provided predictive markers for the development of carotid artery disease within the SSc patient population.

Conclusion. The elevated levels of TNF-{alpha} and thromboxane seen in SSc patient sera are paralleled by increases in the expression of the appropriate genes in leucocytes. This method will allow us to screen for a large number of candidate markers of disease in order to increase our understanding of the processes underlying the pathology of SSc.

KEY WORDS: Transcriptional profiling, Autoimmune disease, Inflammation, Cardiovascular disease, Systemic sclerosis.

Correspondence to: C. N. A. Palmer.

*Present address: The Scottish Crop Research Institute, Invergowrie, UK.


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