Summary
Antiphospholipid antibodies (aPL) may stimulate tissue factor (TF) expression 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 amplification, we have analysed TF mRNA accumulation
in freshly isolated mononuclear blood cells (MBC) of 14 patients with primary APS
(PAPS) and six normal controls. TF mRNA accumulation was low or absent in uncultured
MBC from all normal controls, but was elevated in uncultured MBC from nine of the
patients as well as in normal MBC incubated with 100 ng/ml lipopolysaccharide (LPS).
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 from patients without thrombosis
(N = 5, P = 0.02). Uncultured MBC of patients with thrombosis accumulated TF mRNA
at similar levels to LPS-treated normal MBC. Increased levels of TF mRNA were found
in eight of ten patients with conventional aPL (ie, anti-cardiolipin antibodies [aCL]
and/or lupus anticoagulant [LA]) and littleif any accumulation of TF mRNA was observed
in three of four patients without aPL at the time of study. These data strongly suggest
that circulating monocytes of many patients with PAPS are subjected to an up-regulated
TF expression that may well explain their prothrombotic 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 the 14 patients studied, our study cannot exclude the
involvement of factors other than aCL or LA in inducing TF expression.
Key Words
Antiphospholipid syndrome - in vivo - monocyte - mRNA - tissue factor