title: C4d positivity is often associated with acute cellular rejection in renal transplant biopsies following Campath-1H (Alemtuzumab) induction.
abstract: 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.
authors.affiliation: Division of Laboratory Medicine, Geisinger Medical Center, 100 N. Academy Ave, Danville, PA 17822, USA. plzhang@geisinger.edu
authors.forename: Ping L
authors.initials: PL
authors.lastname: Zhang
authors.forename: Sayeed K
authors.initials: SK
authors.lastname: Malek
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Blasick
authors.forename: Jared R
authors.initials: JR
authors.lastname: Pennington
authors.forename: Kathryn K
authors.initials: KK
authors.lastname: Masker
authors.forename: Mingyue
authors.initials: M
authors.lastname: Lun
authors.forename: Santosh
authors.initials: S
authors.lastname: Potdar
mesh_terms: D000208:Acute Disease; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D015935:Complement C4b / Q000378:metabolism*; D006084:Graft Rejection / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D010446:Peptide Fragments / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015935:Complement C4b; D007166:Immunosuppressive Agents; D018664:Interleukin-12; D010446:Peptide Fragments; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C032261:complement C4d