Increased levels of tissue factor mRNA in mononuclear blood cells of patients with primary antiphospholipid syndrome

Antiphospholipid antibodies (aPL) may stimulate tissue factor (TF) expressi on in cultured endothelial cells and monocytes, but there are discrepancies as to the expression of TF in the patients with antiphospholipid syndrome (APS). By using reverse transcription and polymerase chain reaction amplifi cation, we have analysed TF mRNA accumulation in freshly isolated mononucle ar blood cells (MBC)of 14 patients with primary APS (PAPS) and six normal c ontrols. TF mRNA accumulation was low or absent in uncultured MBC from all normal controls, but was elevated in uncultured MBC from nine of the patien ts as well as in normal MBC incubated with 100 ng/ml lipopolysaccharide (LP S). Mean levels of TF mRNA, as measured by densitometry, were higher in MBC from patients (N = 14) than in those from controls (N = 6, P = 0.009), and in MBC from patients with a history of thrombosis (N = 9) than in those fr om patients without thrombosis (N = 5, P = 0.02). Uncultured MBC of patient s with thrombosis accumulated TF mRNA at similar levels to LPS-treated norm al MBC. Increased levels of TF mRNA were found in eight of ten patients wit h conventional aPL (ie, anti-cardiolipin antibodies [aCL] and/or lupus anti coagulant [LA]) and little if any accumulation of TF mRNA was observed in t hree of four patients without aPL at the time of study. These data strongly suggest that circulating monocytes of many patients with PAPS are subjecte d to an up-regulated TF expression that may well explain their prothromboti c state. Although the presence or absence of TF mRNA in MBC was associated with, respectively, the presence or absence of conventional aPL in 11 of th e 14 patients studied, our study cannot exclude the involvement of factors other than aCL or LA in inducing TF expression.