Desensitization and heart transplantation of a patient with high levels of donor-reactive anti-human leukocyte antigen antibodies.
BACKGROUND
To prepare a highly immunized recipient for heart transplantation, reduction of high levels of cytotoxic antibodies against human leukocyte antigen (HLA) was deemed essential to prevent antibody-mediated graft failure.


METHODS
Antibodies were analyzed by lymphocytotoxic and solid-phase assays. The pretransplant desensitization treatment protocol included daily tacrolimus and mycophenolate mofetil, weekly protein-A immunoadsorption (IA), intravenous immunoglobulin, and daclizumab. Posttransplant treatment consisted of tacrolimus, mycophenolate mofetil, prednisolone, IA, and daclizumab.


RESULTS
During pretransplant desensitization, each of the weekly immunoadsorption treatments reduced anti-HLA antibody levels by 50% to 70%, but they returned to the pretreatment level within 1 week as measured by flow cytometry. Cytotoxic antibodies remained reduced. After perioperative immunoadsorption, the donor-reactive antibodies (DRAs) were reduced to low levels. The patient underwent successful heart transplantation after 6 weeks on a waiting list. During the first week posttransplant, DRAs remained low. However, after the first week, anti-HLA DRAs reappeared and increased slightly over a 3-week period and then decreased slowly. Cytotoxic crossmatches were negative before and 3 week after transplantation. No clinical rejection was encountered. The patient was doing well 3 years after transplantation, and yearly clinical cardiac investigations were all normal. Three hyperimmunized patients have now undergone successful heart transplantation at our center using this desensitization protocol.


CONCLUSIONS
IA in combination with pretransplant immunosuppressive drug treatment temporarily reduces antibody levels. The therapeutic levels of drug treatment at the time of transplantation may be of crucial importance. The treatment protocol resulted in freedom from rejection and other clinical adverse events.
Bućin
Dragan
D
Department of Nephrology and Transplantation, Lund University, Malmö, Sweden. dragan.bucin@skane.se
Gustafsson
Ronny
R
Ekmehag
Björn
B
Kornhall
Björn
B
Algotsson
Lars
L
Lund
Ulla
U
Otto
Gisela
G
Koul
Bansi
B
D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003888:Desensitization, Immunologic / Q000379:methods; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D016060:Sorption Detoxification; D013997:Time Factors; D016896:Treatment Outcome
D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D007519:Isoantigens