ENHANCED PRESENCE OF THROMBOMODULIN IN THE GLOMERULI OF LUPUS GLOMERULONEPHRITIS

The intraglomerular presence of thrombomodulin (TM) was examined in 19 patients with lupus glomerulonephritis (GN). TM is a cell surface gly coprotein found on endothelial cells and plays a key role in the prote in C anticoagulant pathway. Renal biopsy specimens of patients with lu pus GN and several kinds of renal disease other than lupus GN, i.e., m embranous GN, IgA GN, minimal change nephrotic syndrome (MCNS) and hem olytic uremic syndrome (HUS) were examined by indirect immunofluoresce nce, using three kinds of monoclonal antibodies against human TM: KA-2 , KA-3 and KA-4. It has been reported that KA-3 and KA-4 bind to enzym e-digested TM as well as intact TM, while KA-2 recognizes intact TM on ly. In the glomeruli from both normal subjects and patients with MCNS, only very weak staining of TM was found. Patients with HUS showed neg ative TM staining in the glomeruli. In contrast, positive to strongly positive staining of KA-2 as well as of KA-3 and KA-4 was observed mai nly along the capillary wall of glomeruli from patients with lupus GN. Some patients with non-lupus GN showed positive staining of these mon oclonal antibodies, but the staining was far more intense in most pati ents with lupus GN than in the patients with non-lupus GN. Staining of albumin and transferrin by the indirect method was negative in all ca ses of lupus GN that showed positive staining of TM. There was no rela tionship between the intensity of TM staining and the degree of protei nuria, creatinine clearance or histologic types of lupus GN. In conclu sion, the existence of intact TM is enhanced in the glomeruli of patie nts with lupus GN, suggesting that TM plays a role in the regulation o f intraglomerular coagulation in lupus GN.