A NEW ENZYME-LINKED-IMMUNOSORBENT-ASSAY TO MEASURE ANTIENDOTHELIAL ANTIBODIES AFTER CARDIAC TRANSPLANTATION DEMONSTRATES GREATER INHIBITIONOF ANTIBODY-FORMATION BY TACROLIMUS COMPARED WITH CYCLOSPORINE

Background. Chronic rejection or transplant-associated coronary artery disease (TxCAD) is the most serious complication after human cardiac transplantation. Previous studies, using Western blotting, have shown formation of antibodies against endothelial antigens of 56 and 58 kDa, which are associated with early TxCAD, These antigens were later iden tified as being vimentin and its breakdown products. The aims of the p resent study were to devise a robust assay for detection of anti-vimen tin antibodies and to compare antibody formation in patients taking di fferent immunosuppressive drugs. Methods. 106 sequential serum samples from 19 patients taking tacrolimus and 68 sera from 12 patients takin g cyclosporine were examined by enzyme-linked immunosorbent assay (ELI SA) for anti-vimentin antibodies and Western blotting for reactivity a gainst bands at 56/58 kDa, Serum samples were taken before transplanta tion and at 1, 3 6, 9, and 12 months. Results. The vimentin ELISA prod uced significantly higher numbers of positive episodes per patient (3. 92+/-1.08) compared with use of Western blotting (2.54+/-0.52). Serum from patients taking tacrolimus contained significantly less antibodie s measured by ELISA (15.8%) or Western blotting (6.5%) than sera from patients taking cyclosporine (46.8% for ELISA; P=0.001 and 21% by West ern blotting, P=0.01), Intravascular ultrasound performed on six patie nts at 12 months showed a correlation between anti-vimentin antibody f ormation and detection of early coronary disease. Conclusions. The res ults demonstrate first, that differences in antibody profiles produced by different immunosuppressive drugs, and second, that detection of a nti-vimentin antibodies may be a noninvasive method of detecting disea se activity in transplanted vessels.