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J Thorac Cardiovasc Surg 1994;107:1366-1367
© 1994 Mosby, Inc.

LETTERS TO THE EDITOR

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

Department of Surgery
Division of Thoracic and Cardiovascular Surgery
University of Alabama at Birmingham
Birmingham, AL 53294-0007

Reply to the Editor:

The introduction of foreign antigens by means of a transplanted organ results in the generation of a cellular response that is mediated by T lymphocytes and cells of the myeloid lineage. Activation of the humoral arm of the immune response also occurs, and B cells bearing immunoglobulin molecules specific for graft antigens will proliferate and differentiate into plasma cells. The plasma cells secrete large amounts of antibody that will bind to graft antigens and activate a number of inflammatory processes. Current immunosuppressive agents are well suited for suppression of the cellular response because they inhibit T cell activation. However, these agents have been markedly less effective in the suppression of an ongoing humoral immune response. This has proven to be a significant problem in a number of different situations in transplantation, ranging from hyperacute rejection of discordant xenografts to the slow process of "chronic rejection" or graft atherosclerosis. ^{1, 2} Although a number of new drugs, such as deoxyspergualin, are showing promise in the suppression of B cell–mediated responses in transplant recipients, ^3,4 some current strategies for evading humorally mediated organ rejection are oriented toward avoiding the use of donor organs that bear antigens to which the antibodies are specific, or toward the physical removal of antibodies that have been formed. As pointed out in the letter by Ruiz and associates, the use of the former method is not always possible and is certainly even less practical for patients who are likely to have had previous blood transfusions. Thus, Ruiz and associates have attempted to physically remove anti-HLA antibodies by using an affinity column that will specifically adsorb antibodies while leaving most of the plasma components intact. It would be expected that such an approach would be successful providing that the subsequent resynthesis of the anti-HLA antibodies can be successfully inhibited. It is likely that this would depend on the magnitude of the pretransplant humoral immune response, as defined by both the quantity of antibody produced and the average affinity of the antibody molecules.

To determine which population of patients would most likely benefit from immunoadsorption and whether the technique is truly beneficial, a prospective trial must be conducted. A multivariable analysis of the results would show possible risk factors for complications and would facilitate a comparison of the results of immunoadsorption with other treatments such as plasmapheresis and splenectomy.

References

1. Platt JL, Bach FH. Discordant xenografting: challenges and controversies. Curr Opin Immunol 1991;3:735-9.[Medline]
   
2. Hosenpud JD, Shipley GD, Wagner CR. Cardiac allograft vasculopathy: current concepts, recent developments, and future directions. J Heart Lung Transplant 1992;11:9-23.[Medline]
   
3. Tepper MA, Petty B, Bursuker I, et al. Inhibition of antibody production by the immunosuppressive agent, 15-deoxyspergualin. Transplant Proc 1991;23:328-31.[Medline]
   
4. Takahashi K, Tanabe K, Ooba S, et al. Prophylactic use of a new immunosuppressive agent, deoxyspergualin, in patients with kidney transplantation from ABO-incompatible or preformed antibody positive donors. Transplant Proc 1991;23:1078-82.[Medline]
   

This article has been cited by other articles:

				S. Itescu, T. C. Tung, E. M. Burke, A. Weinberg, N. Moazami, J. H. Artrip, N. Suciu-Foca, E. A. Rose, M. C. Oz, and R. E. Michler Preformed IgG Antibodies Against Major Histocompatibility Complex Class II Antigens Are Major Risk Factors for High-grade Cellular Rejection in Recipients of Heart Transplantation Circulation, August 25, 1998; 98(8): 786 - 793. [Abstract] [Full Text] [PDF]

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