Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries

Details

Serval ID
serval:BIB_6C3F52599073
Type
Article: article from journal or magazin.
Collection
Publications
Title
Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries
Journal
Journal of the American Society of Nephrology
Author(s)
Collins  A. B., Schneeberger  E. E., Pascual  M. A., Saidman  S. L., Williams  W. W., Tolkoff-Rubin  N., Cosimi  A. B., Colvin  R. B.
ISSN
1046-6673
Publication state
Published
Issued date
10/1999
Peer-reviewed
Oui
Volume
10
Number
10
Pages
2208-14
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct
Abstract
The distinction between acute humoral rejection (AHR) and acute cellular rejection (ACR) in renal allografts is therapeutically important, but pathologically difficult. Since AHR is probably mediated by antibodies to the donor endothelium that activate the classical complement pathway, it was hypothesized that peritubular capillary C4d deposition might distinguish this group. Renal biopsies (n = 16) from 10 patients with AHR who had acute graft dysfunction, neutrophils in peritubular capillaries, and a concurrent positive cross-match were stained for C4d by immunofluorescence. Control biopsies for comparison showed ACR (n = 14), cyclosporin A toxicity (n = 6), or no abnormality (n = 4). Peribiopsy sera were tested for anti-donor HLA antibody. C4d deposited prominently and diffusely in the peritubular capillaries in all AHR biopsies (16 of 16). IgM and/or C3 were also present in 19 and 44%, respectively. With two-color immunofluorescence, C4d was localized in basement membranes (type IV collagen+) and in the endothelium (Ulex europaeus agglutinin-I+). In ACR, no more than trace C4d was found in peritubular capillaries (P < 0.0001 versus AHR), and no patient had anti-donor HLA antibodies (0 of 8); 27% had neutrophils in peritubular capillaries. One of six biopsies with cyclosporin A toxicity had similar C4d deposits, and circulating anti-donor class I antibody was detected. Grafts with AHR were lost (40%) more often than those with ACR (0%; P < 0.02). C4d in peritubular capillary walls distinguishes AHR from ACR, is more specific and sensitive than traditional criteria, and is a potentially valuable adjunct in the diagnosis of graft dysfunction.
Keywords
Acute Disease Antibody Formation/physiology Antigens, CD4/*analysis Biopsy, Needle Capillaries/immunology Complement Activation/*immunology Female Graft Rejection/*immunology Humans Immunity, Cellular/physiology Kidney/*pathology Kidney Transplantation/adverse effects/*immunology/*pathology Kidney Tubules/blood supply/immunology Male Microscopy, Fluorescence Reference Values
Pubmed
Web of science
Create date
29/01/2008 13:53
Last modification date
20/08/2019 14:26
Usage data