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Annals of Clinical & Laboratory Science 37:121-126 (2007)
© 2007 Association of Clinical Scientists

C4d Positivity Is Often Associated with Acute Cellular Rejection in Renal Transplant Biopsies Following Campath-1H (Alemtuzumab) Induction

Ping L. Zhang1,2, Sayeed K. Malek3, Thomas M. Blasick2, Jared R. Pennington3, Kathryn K. Masker2, Mingyue Lun2 and Santosh Potdar3
1 Division of Laboratory Medicine, 2 Weis Center for Research, and 3 Department of Transplantation and Liver Surgery, Geisinger Medical Center, Danville, Pennsylvania

Address correspondence to Ping L. Zhang, MD, PhD, Division of Laboratory Medicine, Geisinger Medical Center, 100 N. Academy Ave, Danville, PA 17822, USA; tel 570 271 6333; fax 570 271 6105; e-mail plzhang{at}geisinger.edu.

Peritubular capillary C4d positivity, a marker for antibody-mediated rejection, is observed in approximately 20–50% of indicated renal transplant biopsies and in just 2% of unremarkable protocol biopsies. However, C4d staining has not been evaluated in protocol renal biopsies from patients with Campath-1H induction treatment, and the association between various types of inflammatory cells and acute antibody-mediated rejection is unclear. This study investigated the rates of C4d positivity in unremarkable protocol renal biopsies, biopsies with acute tubular necrosis (ATN), and biopsies with acute cellular rejection (ACR), all following Campath-1H treatment and post-operative immunosuppression. There was low positivity of C4d staining in both the protocol and ATN groups, but the ACR group had a 47.2% rate of positivity (combining focal and diffuse positive cases). Since Campath-1H treatment caused significant depletion of circulating lymphocytes but not circulating monocytes in renal recipients, this study also investigated the role of monocytes in humoral rejection. In ACR cases, CD68 positive monocytes were composed of 59.4 ± 4.69% inflammatory cells, which was significantly higher than CD3 positive lymphocytes (38.9 ± 4.4%). Co-localization of positive C4d staining in endothelium and marginating CD68 positive monocytes was illustrated by double staining. Our data indicate that acute antibody-mediated rejection occurs much more frequently in renal transplants with ACR. Moreover, the high percentage of monocytes observed in ACR cases (due to monocytes being less sensitive to Campath-1H depletion) suggests that monocytes are involved in antibody-mediated rejection.

Keywords: Campath-1H, Alemtuzumab, antibody mediated rejection, renal transplantation






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