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 patients) the expression of both LFA-1 and VLA-4 leukocyte adhesion receptors 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 integrin VLA-4 and the activation signal AIM/CD69 (activation inducer molecule) on interstitial cells were significantly (P < 0.001) higher in rejection than in nephrotoxicity. A main differential expression pattern was observed for VCAM-1, the endothelial cell ligand of VLA-4. Interestingly, a strong staining pattern of the renal vascular endothelium and 35% of tubular epithelium was obtained with anti-VCAM-1 antibody in rejection, as compared with a weak reactivity in endothelium and discrete 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 nephrotoxicity. Nevertheless, a discrete significant (P < 0.05) "de novo" expression of ICAM-1 was present on tubular cells during rejection. Our results strongly suggest that in rejection the interstitial cell infiltrate 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 leukocyte interaction does not play a role in cases with CsA nephrotoxicity. Furthermore, the differential expression patterns of VLA-4 and VCAM-1 molecules found between rejection and CsA nephrotoxicity could provide valuable immunohistochemical criteria in the diagnosis of allograft dysfunction.