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J Thorac Cardiovasc Surg 1994;107:1366
© 1994 Mosby, Inc.

LETTERS TO THE EDITOR

Successful heart transplantation after anti-HLA antibody removal with protein-A immunoadsorption in a hyperimmunized patient

Nephrology Service^a

To the Editor:

Human leukocyte antigen (HLA) sensitization resulting from loss of previous transplants, blood transfusions, or pregnancies is a recognized problem in kidney transplantation, because it decreases the chances of finding crossmatch-negative donors to potential graft recipients Although this situation is rarely encountered in heart transplantation, it may represent a clinical problem because of the limited time available for a suitable graft. Successful kidney transplantation at peak positive, current negative crossmatch after anti-HLA antibody removal has been reported, with protein-A immunoadsorption. ^{1, 2} A full description of this new technique with indications and results can be found in an extensive review published by Gjörstrup and Watt. ³ The technique has now been applied for the first time to allow heart transplantation in a highly sensitized recipient.

The patient was a 49-year-old man with aortic valve insufficiency who underwent an aortic valve replacement with a bioprosthesis. During the operation he received 7 units of blood. This attempt at correction failed and his dilated cardiomyopathy gradually worsened. Two years later he was accepted into the heart transplant program. However, two consecutive donor-specific crossmatches were positive and the patient did not receive the transplant. Serologic investigations showed that the patient's serum reacted with more than 80% of the cells in a random donor panel (20 cells) according to standard lymphocytotoxicity testing. The only known cause for his sensitization was the blood transfusions given at the previous operation.

It was decided to try to remove the anti-HLA antibodies by immunoadsorption. The patient's plasma was specifically deprived of immunoglobulins by means of a column containing protein-A Sepharose (Immunosorba Protein-A and CITEM 10, EXCORIM, Lund, Sweden) and later returned to the patient together with the previously separated blood cells, avoiding the need for replacement fluids. Eleven sessions of immunoadsorption were performed during a period of 35 days. The treatment was well tolerated. The serum level of immunoglobulin G decreased from 14.2 to 0.7 gm/L and that of immunoglobulin M from 1.7 to 0.2 gm/L. Concomitantly with the reduction of the immunoglobulin level, the panel reactivity was completely abolished from the initial level of 80%. One day after the last session of immunoadsorption the patient underwent transplantation of a donor-specific negative crossmatch. Crossmatch performed with sera obtained immediately before immunoadsorption (thus, before antibody removal) was positive, indicating that the current negative crossmatch was a result of immunoadsorption. The operation and immediate postoperative period were uneventful. No clinical signs of rejection were detected (immunosuppressive therapy included cyclosporine, azathioprine, prednisone, and OKT3) and heart function was normal. However, 28 days after transplantation a fulminant septicemia developed as a result of Pseudomonas aeruginosa (with origin in a wound infection), and he died. Postmortem histologic studies showed normal heart tissue without any signs of rejection.

Transplantation in the hyperimmunized patient is known to be associated with poorer graft outcome than that in the nonimmunized patient, both in kidney and in heart transplant recipients. ^{4, 5} According to the policy at our hospital, the warm crossmatch must be negative for heart transplantation to be done (autoantibodies being excluded). Assuming that the positive preimmunoadsorption crossmatch had been the current one (without the antibody removal), the patient would not have received the graft that he received. This experience with immunoadsorption shows that heart transplantation is possible after removal of anti-HLA antibodies. The lack of clinical and histologic signs of rejection in our patient shows the immunoadsorption protocol and transplantation to be successful from an immunologic point of view. Despite the fact that the patient died of an incurable infection, we are encouraged by this first experience and think that immunoadsorption should increase the possibilities for transplantation in potential hyperimmunized heart transplant recipients, as has previously been successfully demonstrated in kidney transplantation.

References

1. Palmer A, Welsh K, Gjörstrup P, Taube D, Bewick M, Thick M. Removal of anti-HLA antibodies by extracorporeal immunoadsorption to enable renal transplantation. Lancet 1989;1:10-2.[Medline]
   
2. Gjörstrup P. Anti-HLA antibody removal in hyperimmunized ESRD-patients to allow transplantation. Transplant Proc 1991;23:392-5.[Medline]
   
3. Gjörstrup P, Watt RM. Therapeutic protein A immunoadsorption: a review. Transfusion Sci 1990;11:281-320.
   
4. Turka LA, Goguen JE, Cagne JE, Milford EL. Presensitization and the renal allograft recipient. Transplantation 1989;47:234-40.[Medline]
   
5. Lavee J, Kormos RL, Duquesnoy RJ, et al. Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation. J Heart Lung Transplant 1991;10:921-9.[Medline]
   

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