EXPRESSION OF ADHESION MOLECULES IN ALLOGRAFT RENAL DYSFUNCTION - A DISTINCT DIAGNOSTIC PATTERN IN REJECTION AND CYCLOSPORINE NEPHROTOXICITY

We have studied in thirty renal biopsies (from 30 cadaver allograft pa tients) the expression of both LFA-1 and VLA-4 leukocyte adhesion rece ptors and their respective ICAM-1 and VCAM-1 endothelial cell ligands, during early allograft dysfunction (24+/-5 days after transplantation ), reversed either by antirejection therapy (n=14) or by reduction in CsA dose (n=16). We have found that the levels of expression of the in tegrin VLA-4 and the activation signal AIM/CD69 (activation inducer mo lecule) on interstitial cells were significantly (P<0.001) higher in r ejection than in nephrotoxicity. A main differential expression patter n was observed for VCAM-1, the endothelial cell ligand of VLA-4. Inter estingly, a strong staining pattern of the renal vascular endothelium and 35% of tubular epithelium was obtained with anti-VCAM-1 antibody i n rejection, as compared with a weak reactivity in endothelium and dis crete staining pattern on tubules in nephrotoxicity. On the other hand , we found that the mean percentage of infiltrating cells bearing LFA- 1 molecules and the intensity of ICAM-1 (a LFA-1 ligand) expression on endothelium were closely similar in both rejection and CsA nephrotoxi city. Nevertheless, a discrete significant (P<0.05) ''de novo'' expres sion of ICAM-1 was present on tubular cells during rejection. Our resu lts strongly suggest that in rejection the interstitial cell infiltrat e seems to be facilitated by the contribution of both LFA-1/ICAM-1 and VLA-4/VCAM-1 cell adhesion mechanisms, and also that VLA-4/VCAM-1 leu kocyte interaction does not play a role in cases with CsA nephrotoxici ty. Furthermore, the differential expression patterns of VLA-4 and VCA M-1 molecules found between rejection and CsA nephrotoxicity could pro vide valuable immunohistochemical criteria in the diagnosis of allogra ft dysfunction.