Increase in plasma thrombomodulin in lupus erythematosus with antiphospholipid antibodies.

Thrombomodulin (TM), a high-affinity thrombin receptor present on endothelial cell membrane,’ plays an important role as a natural anticoagulant. It acts as a cofactor of thrombin-catalyzed activation of protein C, and it also inhibits procoagulant functions of t h r ~ m b i n ? ~ Soluble TM exists in circulating plasma as heterogeneous fragments? Plasma TM has been found increased in renal dysfunction, disseminated intravascular coagulation, pulmonary thromboembolism, adult respiratory distress syndrome, and acute hepatic f a i l ~ r e . ~ It is regarded as a molecular marker reflecting injury of endothelial cells.6 A close relationship between TM and diabetic microangiopathy has recently been shown.‘ Information concerning TM plasma levels in systemic lupus erythematosus (SLE) is not currently available. Using a two-site enzyme-linked immunosorbent assay (ELISA) for soluble forms of TM (“Asserachrom Thrombomodulin,” Diugnosticu Stugo, AsniBres, France), prepared with two monoclonal antihuman TM antibodies, we investigated plasma TM levels in 40 normal adult blood donors and in 45 SLE patients. The patients were selected to have a normal creatinine level of less than 100 pmol/L because renal impairment per se is known to be associated with an increase in TM.5,’ Antiphospholipid antibodies (APL) were assessed by an ELISA according to Harris? We studied IgG and IgM antibodies directed against anionic phospholipids (mixture of cardiolipin/phosphatidylserine/phosphatidylinositol/phosphatidylglycerol/phosphatidic acid) and against phosphatidylethanolamine. The SLE patients were divided into two groups according to the absence (group 1) or presence (group 2) of APL and/or lupus anticoagulant (LA). Twenty SLE patients without APL or LA were included in the group 1. Twenty-five patients were included in group 2: 15 had both APL and LA, 9 had APL without LA, and 1 had an isolated LA. The number of patients suffering from thrombosis and/or recurrent fetal loss is given in Table 1. In agreement with previous study on systemic lupus erythematosus: occurrence of thrombosis and recurrent fetal loss was significantly