IMMUNOEXPRESSION OF ADHESION MOLECULES AND INFLAMMATORY CELL Profile in VASCULAR LESIONS of TYPE III ACUTE REJECTION OF THE RENAL ALLOGRAFT

Soares m.f., Medina-Pestana J.O., Franco m.f..

Division of Pathology. Federal University of São Paulo (UNIFESP). São Paulo, São Paulo, Brazil.
 

Objectives: Acute tubulo-interstitial and mild vascular rejection are tipically T-cell mediated processes. Acute severe vascular rejection (Banff type III) however may be mediated by receptor antibodies directed to donor cells and is histologically characterized by transmural arteritis and/or fibrinoid necrosis of the vessel wall. It is still object of debate if transmural arteritis and fibrinoid necrosis are pathogenetically distinct entities. This study tries to shed some light over this question by analyzing the immunoexpression of adhesion molecules and the inflammatory cell profile in renal allografts with type III rejection.

Methods: Seventy explanted renal allografts with acute severe vascular rejection were analyzed. Vascular lesions were classified as i) “FN”- fibrinoid necrosis; ii) “TA”- transmural arteritis and iii) “M”- mixed fibrinoid necrosis and transmural arteritis. Formalin-fixed, paraffin-embeded tissue underwent immunoperoxidase testing for: i) Presence of CD4, CD8, CD20 and CD68 in vessel wall and interstitial inflammatory cells; ii) Positivity for C4d in peritubular capillaries; iii) Presence of ICAM-1 and VCAM-1 in vessel wall. Groups were compared by Fisher Exact Test, with p=0.005, corrected by Bonferroni in multiple comparisons (p=0,018).

Results: Statistically significant differences were observed in: I) The presence of CD4 and CD8-positive lymphocytes and CD68-positive hystiocytes in vessel walls was higher in TA and M lesions than in FN lesions; II) Endothelial and arterial tunica media positive immunoexpression of ICAM-1 and VCAM-1 was more consistently observed in TA and M lesions than in FN lesions. Among the tested groups, no statistically significant differences were registered regarding C4d positivity in peritubular capillaries and the positivity of the tested markers in interstitial inflammatory cells.

Conclusions: The results suggest that T-cell interactions are involved in the increased positivity of vascular adhesion molecules ICAM-1 and VCAM-1 in type III renal allograft rejection. The peritubular capillary C4d positivity in the three patterns of lesions  indicated that both transmural arteritis and fibrinoid necrosis have an antibody-mediated injury mechanism.