Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction.
BACKGROUND
The goal of this study was to determine whether the production of posttransplant antibodies directed against donor HLA mismatches (donor specific antibody; DSA) is associated with renal allograft rejection and early graft dysfunction.


METHODS
Forty-nine adult renal allograft recipients with increased risk of rejection were enrolled during the period of October 2001 through May 2003 and were prospectively monitored for the development of anti-HLA antibodies.


RESULTS
Of 49 patients, eight (16.3 %) patients were diagnosed with acute humoral rejection (AHR) and 11/49 (22.4%) patients were diagnosed with acute cellular rejection (ACR). A strong association between pretransplant HLA sensitization and AHR was found (P=0.005). Of the eight patients diagnosed with AHR, the majority developed DSA before or concomitant with episodes of rejection (P<0.001). Only 3 of 41 patients (7.3%) without AHR developed DSA. The pathogenic role of alloantibodies was further substantiated by analyzing their association with graft function as measured by serum creatinine levels. The average serum creatinine after the third month posttransplantation in DSA producers was 2.24+/-1.01 mg/dL, while in non-DSA patients the average serum creatinine was 1.41+/-0.37 mg/dL (P<0.01).


CONCLUSIONS
This study reveals a strong association between the production of DSA, AHR, and early graft dysfunction. Our findings indicate that prospective monitoring for anti-HLA antibodies following transplantation is a useful test for the diagnosis and classification of AHR for identifying patients at risk of early graft dysfunction.
Zhang
Qiuheng
Q
UCLA Immunogenetics Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Liang
Leonard W
LW
Gjertson
David W
DW
Lassman
Charles
C
Wilkinson
Alan H
AH
Kendrick
Elizabeth
E
Pham
Phuong-Thu T
PT
Danovitch
Gabriel M
GM
Gritsch
H Albin
HA
Reed
Elaine F
EF
D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000209:etiology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
D006680:HLA Antigens; D007518:Isoantibodies