The Significance of Adhesion Molecules and Granzyme B in Acute Renal Allograft Rejection

Park, So Yeon; Kim, Hwal Woong; Lee, Hyun Soon

Abstract

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are weakly expressed in normal glomerular cells and vascular endothelial cells, but not in tubules. Granzyme B is a cytotoxic granule present in activated cytotoxic T cells and natural killer cells. To determine the effect of ICAM-1 and VCAM-1 expression and granzyme B-positive cells on histologic grade of rejection, we performed the immunohistochemical study on 19 renal biopsy specimens and one nephrectomy specimen from 14 patients with acute renal allograft rejection using monoclonal antibodies against theses proteins. According to severity of rejection based on Banff classification, three biopsies were classified as borderline, 4 grade I, 12 grade II, and 1 grade III. In all the cases with acute rejection, ICAM-1 and VCAM-1 were expressed in the tubular epithelial cells. The numerical score of ICAM-1 in the tubular epithelial cells was 1.0 in borderline cases, 1.3 0.4 in grade I cases, 2.2 0.8 in grade II cases, and 3.0 in grade III case. The staining intensity of ICAM-1 in the tubular epithelial cells was increased in accordance with histologic rejection grade (P<0.05). The staining intensity of ICAM-1 and VCAM-1 in the renal tubular epithelial cells was increased in accordance with the number of T lymphocytes in the renal parenchyme (r=0.46; P<0.05, r=0.61; P<0.01). The number of granzyme B-positive cells was 6.4 1.6/HPF in borderline cases, 8.1 2.5 in grade I cases, 19.6 11.7 in grade II cases, and 53 in grade III case. The number of T lymphocytes and granzyme B-positive cells was also increased in accordance with histologic rejection grade (P<0.05). These results suggest that ICAM-1 and granzyme B-positive cells may play an important role in the induction of renal allograft rejection and that the grading of severity of these parameters may be useful to predict the prognosis of renal allograft.