Formation of donor-specific human leukocyte antigen antibodies after kidney transplantation: correlation with acute rejection and tapering of immunosuppression.
BACKGROUND
Before kidney transplantation, a serological crossmatch is routinely performed between donor and recipient to prevent hyperacute rejection by donor-specific anti-human leukocyte antigen (HLA) antibodies. After transplantation, the presence of these antibodies is not routinely monitored. We wanted to know whether donor-specific anti-HLA antibodies are detectable during acute rejection (AR), before or after reduction of immunosuppression in kidney transplant recipients who were converted from cyclosporine A (CsA) to the less nephrotoxic azathioprine (AZA) or mycophenolate mofetil (MMF) at 1 year after transplantation.


METHODS
Plasma samples were collected before transplantation, at several time points after transplantation, and during AR. Antibodies were measured in 29 patients: 5 patients with AR during the first year after transplantation (before conversion), 14 patients with AR after conversion or dose-reduction of AZA or MMF, and a control group of 10 patients without AR during a follow-up of 2 years (1 year before and 1 year after conversion of immunosuppression). Antibodies were measured by complement-dependent cytotoxicity assay, enzyme-linked immunosorbent assay (ELISA), and flow-cytometry in a crossmatch with donor spleen cells.


RESULTS
Donor-specific antibodies were not detectable after transplantation in the control group without AR, nor in patients with AR shortly after transplantation during CsA therapy. After conversion from CsA to AZA or MMF, antibodies appeared only in one patient after graft failure followed by transplantectomy and in patients during AR on AZA but not on MMF therapy.


CONCLUSIONS
In this patient group, we could not detect donor-specific antibodies during CsA treatment, not even at the time of AR using three different techniques. Donor-specific antibodies were primarily present during AR in patients converted from CsA to AZA and were not found in the sera from patients converted to MMF.
van der Mast
Barbara J
BJ
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. b.vandermast@erasmusmc.nl.
van Besouw
Nicole M
NM
Witvliet
Marian D
MD
de Kuiper
Petronella
P
Smak Gregoor
Peter
P
van Gelder
Teun
T
Weimar
Willem
W
Claas
Frans H J
FH
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D001379:Azathioprine / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine