Beyond histology: lowering human leukocyte antigen antibody to improve renal allograft survival in acute rejection.
BACKGROUND
The common endpoint in the treatment of antibody-mediated rejection (AMR) is functional reversal (creatinine levels). Reduction of human leukocyte antigen (HLA) antibody strength is not commonly considered as an essential endpoint for AMR resolution. The purpose of this study was to determine whether reduction in HLA antibody intensity in patients with histologic AMR reversal influences long-term renal allograft survival.


METHODS
Renal allograft recipients were included if he or she had a biopsy diagnosis of AMR (between August 2000 and October 2008) and serial evaluation for HLA antibodies prebiopsy and postbiopsy. Antibody reduction was defined as mean fluorescence intensity decrease more than 50% in highest intensity antibody after AMR therapy and the absence of new antibody formation. Patients were treated with plasmapheresis, thymoglobulin/OKT3, and corticosteroids. Survival analysis was performed using STATA/MP v10 (College Station, TX).


RESULTS
Twenty-eight patients were analyzed. Antibody reduction failed to occur in 22 of 28 cases. Baseline characteristics were similar between groups. Antibody nonresponders had significantly shorter allograft survival time (61.4 months) compared with antibody responders (no failures) (P=0.04, log-rank test).


CONCLUSIONS
In conclusion, failure to significantly reduce antibody levels and prevent new formation was strongly predictive of allograft loss. This observation suggests that the therapeutic intervention that reduces antibody production may prolong graft survival in transplantation.
Everly
Matthew J
MJ
Terasaki Foundation Laboratory, Los Angeles, CA 90064, USA. meverly@terasakilab.org
Rebellato
Lorita M
LM
Ozawa
Mikki
M
Briley
Kimberly P
KP
Catrou
Paul G
PG
Haisch
Carl E
CE
Terasaki
Paul I
PI
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000917:Antibody Formation; D000961:Antilymphocyte Serum; D001706:Biopsy; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000096:biosynthesis / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D010956:Plasmapheresis; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016853:Muromonab-CD3; C512542:thymoglobulin