The Expression of C4d and CD20 in Graft Kidney with Acute Rejection

Kim, Ji Hwan; Oh, Hyae Ju; Son, Young Ki; Park, Yong Ki; Sin, Yong Hun; Kim, Joong Kyung; Kang, Won Geun; Lee, Sang Su; Hur, Kill; Chang, Hee Kyung

Abstract

PURPOSE: The presence of C4d in peritubular capillaries (C4d (PTC)) as a diagnostic in-situ marker of acute humoral rejection and CD20 as marker of B-cell deposition in graft kidney has been reported to be related to steroid resistance and poor outcome. In this retrospective study, we evaluated the clinical significance of C4d and CD20 in allograft renal biopsies by immunohistochemistry technique. And we also evaluated the relationships between C4d and CD20 positive B lymphocytes.
METHODS
We studied 22 patients who had been biopsied for suspected acute rejection. Biopsies were classified by updated Banff 97 criteria. Of the 22 cases, borderline rejection and Banff 1A were 11 cases respectively and no case had a vascular lesion. Paraffin sections were stained with monoclonal antibodies (anti-C4d and -CD20) using an immunohistochemistry technique and the results of immunohistochemistry were analyzed by clinical data.
RESULTS
Of the 22 cases, 22.7% (5/22) showed diffuse and 40.9% (9/22) showed focal C4d positivity in peritubular capillaries. The grafts failed to survive in 20% (1/5) of the diffuse (P), 44.4% (4/9) of the focal, and 0% (0/8) of the negative group for 2 years since postbiopsies, however, the C4d staining was not statistically related to graft loss and graft survival rates (P=0.091, P=0.106 respectively). The C4d positivity was significantly related to the level of serum creatinine (P=0.042) and to steroid pulsing therapy resistance (P=0.030). However C4d deposition was not associated with recipient gender, age, type of donor (living vs deceased), HLA matching, induction, and Banff classification. On the CD20 immunostaining, 50.0% (11/22) showed negative reactivity, 9.1% (2/22) one nodule, 40.9% (9/22) 2 nodules. The presence and the number of CD20 positive nodules were not correlated to the C4d clinical data. But, the degree of C4d staining was statistically related with the presence of CD20 positive nodules (P=0.029).
CONCLUSION
The peritubular capillary C4d is clinically important however, not likely a significant predictor of grafts survival rates in mild rejection. The clinical implication of CD20 positive B lymphocyte nodules in acute rejection was not demonstrated in this study. But, CD20 positive B lymphocyte may be a positive linkage with C4d and participate in humoral rejection.