Elevated expression of the genes encoding TNF-α 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 gamma, low-density lipoprotein-associated lipoprotein lipase A(2) (LDL-PLA(2)), apolipoprotein E (apoE) and cholesterol 27-hydroxylase (CYP27). Results. Both TNF-alpha and TXAS showed art 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.