Clinical significance of serum thrombomodulin levels in patients with systemic rheumatic diseases

Objective. To determine the soluble thrombomodulin (TM) level in the sera of patients with systemic rheumatic diseases and to analyze its relationship with clinical and laboratory parameters in patients with systemic lupus erythematosus (SLE). Methods. Serum levels of TM were measured by an enzyme-linked immunosorbent assay in 124 patients with SLE and in 237 patients with systemic rheumatic diseases other than SLE. Results. The frequency of patients with high TM levels (greater than or equal to 4.5 FU/ml) was 21% in SLE, 16% in rheumatoid arthritis (RA), 12% in Sjogren's syndrome (SS), and 4% in systemic sclerosis (SSc). The TM levels were significantly higher in SLE patients with the following abnormalities in their past history or present illness: persistent proteinuria, cellular casts, positive anti-dsDNA antibodies (p < 0.001), hypoalbuminemia, decreased creatinine clearance (Ccr), positive anti-Sm antibody, positive immune complex, leukopenia (p < 0.01), pericarditis, oral ulcer, fluorescent anti-nuclear antibody (FANA), decreased C3 and arthralgia (p < 0.01), and an inverse correlation with the serum albumin level (p < 0.01) and complement C3 level (p < 0.05). In SLE patients with active disease, the median TM level at the time of admission (5.9 FU/ml) was significantly higher than at 6 months before admission (3.8 FU/ml, p < 0.01) and at 6 months after admission (4.2 FU/ml, p < 0.001). Moreover, elevation and reduction of the TM level in lupus patients with active disease parallelled that of the SLE disease activity index (SLEDAI). In two representative SLE cases, one with lupus nephritis (LN) and the other with thrombocytopenia without LN, elevated TM levels at disease flare were reduced along with the amelioration of the disease by administration of corticosteroids. Conclusions. The serum TM level is closely associated with SLE activity and appears to be useful as a new disease activity parameter of SLE.