Characteristics of donor-specific anti-HLA antibodies and outcome in renal transplant patients treated with a standardized induction regimen.
Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients.



Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology. DSA with mean-fluorescence intensity (MFI) values above 500 were considered positive. All recipients received basiliximab induction and tacrolimus-based maintenance immunosuppression. DSA were monitored post-transplantation in patients with pre-transplant DSA. Antibody results were correlated with the incidence of rejection and graft loss.



In total, 61/174 patients had pre-transplant DSA. We found a strong correlation between the presence of DSA against class I and II HLA and DSA MFI greater than 10 000. Both DSA patterns independently predicted an increased risk of early AMR (odds ratio 4.24 and 4.75, respectively, P < 0.05). The risk for AMR in patients with intermediate MFI (3000-10 000) gradually increased with increasing MFI but group sizes were too small to allow for final conclusions. The risk for AMR was comparable to nonsensitized patients in patients with only class I or II HLA-DSA or MFI below 3000. 5-year allograft survival was lowest in patients with simultaneous presence of class I and II HLA-DSA and MFI above 10 000 (45%) but was comparable between patients with only HLA class I or II or no DSA (90.0, 90.0 and 88.1%, respectively). AMR was the only independent predictor of graft loss. Undetectable DSA 14 days post-transplant predicted excellent long-term outcome.



. The favourable outcome in the majority of DSA-positive patients despite non-depleting antibody induction and the poor outcome in patients with class I and II HLA-DSA and high DSA strength call for a differentiated therapeutic approach in this patient population.
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Daniel
D
Zecher
Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Christian
C
Bach
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Christoph
C
Staudner
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Carsten A
CA
Böger
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Tobias
T
Bergler
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Bernhard
B
Banas
Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Bernd M
BM
Spriewald
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies
allograft survival; antibody-mediated rejection; donor-specific antibodies; induction therapy; kidney transplantation