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

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 ?, 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? 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.