Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts.
BACKGROUND
Although the incidence of early acute rejection could have been diminished in the past, the long-term renal allograft survival could not benefit from the introduction of more effective immunosuppressive regimens mainly aiming at cellular rejection mechanisms. The cause of chronic rejection is still discussed controversially. Here, we demonstrate to what extent human leukocyte antigen (HLA) antibodies (HLAab) posttransplant contribute to late graft outcome.


METHODS
A total of 1014 deceased kidney transplant recipients transplanted at the Charité hospital were monitored in a cross-sectional manner for the development of HLAab using Luminex Single Antigen beads. Patients with stable kidney function at a median of 5-years posttransplant were tested once for HLAab and monitored for 5.5 years after testing.


RESULTS
Thirty percent of recipients showed HLAab. Donor-specific antibodies (DSA) were found in 31% of antibody positive patients. The presence of DSA was associated with a significantly lower graft survival of 49% vs. 83% in the HLAab negative group (P< or =0.0001). Non-DSAs also had an adverse effect on graft survival (70% vs. 83%; P=0.0001). In a prospective analysis of 195 patients with repeatedly no detectable HLAab, the survival probability was 94% as opposed to 79% survival among patients who developed HLAab de novo after the first testing (P=0.05).


CONCLUSIONS
We confirmed that HLAab produced even late after transplantation are detrimental to graft outcome. DSA were proven to have a strong adverse impact on graft survival. The results indicate that a posttransplant HLAab monitoring routine could be appropriate to improve long-term results.
Lachmann
Nils
N
Charité-Universitätsmedizin Berlin, Center for Tumor Medicine, HLA-Laboratory CampusVirchow-Klinikum, Berlin, Germany. nils.lachmann@charite.de
Terasaki
Paul I
PI
Budde
Klemens
K
Liefeldt
Lutz
L
Kahl
Andreas
A
Reinke
Petra
P
Pratschke
Johann
J
Rudolph
Birgit
B
Schmidt
Danilo
D
Salama
Abdulgabar
A
Schönemann
Constanze
C
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology*; D006680:HLA Antigens / Q000097:blood* / Q000276:immunology*; D015234:HLA-A Antigens / Q000097:blood; D015235:HLA-B Antigens / Q000097:blood; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D015415:Biomarkers; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D003404:Creatinine