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Immunological Assessment of the Transplant Patient

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Kidney Transplantation

Abstract

The main objective of this chapter is to provide an overview of the immunological evaluation of all potential kidney transplant recipients. The discussion begins with the various immunologic barriers to transplantation, including ABO blood group differences, circulating anti-donor human leukocyte antigen (HLA) antibodies from previous antigen exposure, and minor histocompatibility antigens, which is why even HLA-identical siblings require at least some immunosuppression. Another important concept for readers to grasp is that allograft survival is related to the number of HLA matches. A greater degree of HLA mismatches is also related to higher rates of rejection, which underscores the importance of testing recipients for the presence of preformed antibodies against potential donor HLA antigens.

The remaining sections of the chapter describe the several laboratory assays that form the cornerstone of pretransplant testing in potential kidney transplant recipients. The first test is a determination of the breadth of antibodies that an individual possesses, commonly referred to as the panel reactive antibody (PRA) test. This assay involves the use of as many Class I and II HLA antigens as possible to determine the reactivity of an individual to various HLA antigens, expressed as a percentage. If the PRA for Class I or II is above 0 %, a more specific test using single antigen beads is used to determine the identity and strength of an antibody. Once an antibody is identified and the corresponding HLA antigen is deemed unacceptable for a potential recipient by his/her transplant center, the center then reports this as an unacceptable antigen to the United Network for Organ Sharing (UNOS) computer program UNet. Kidneys that possess an unacceptable HLA antigen become unavailable to the recipient. UNOS collects this information in UNet, and the combination of unacceptable antigens results in a calculated PRA (cPRA) for each individual, which can affect his/her waiting time for a kidney transplant.

Pretransplant crossmatch tests are performed prior to transplant to determine whether a donor’s kidney will be acceptable for a recipient. The standard complement-dependent cytotoxicity (CDC) crossmatch is an older method which uses donor cells mixed with recipient serum and complement to determine if the antibodies in the serum will lead to donor cell damage via the complement attack complex. The presence of damaged donor cells indicates a positive crossmatch between the donor and recipient, making the transplant at risk for hyperacute or acute rejection. The flow crossmatch is the more recent method used in performing pretransplant crossmatches. This method involves mixing donor lymphocytes with patient serum and fluorochrome-tagged anti-human globulin. The cells are run through a flow cytometer which detects cells that have the attached patient antibody and fluorochrome-tagged anti-human globulin. If the flow cytometer detects cells with antibody and the tagged anti-human globulin, it is considered a positive flow crossmatch, indicating that the recipient has an antibody directed against the donor HLA antigen, known as a donor-specific antibody (DSA). Further lab tests are done to determine the specific antibody and the level of antibody present. In summary, at the end of this chapter the reader should have a basic understanding of the pretransplant immunologic evaluation.

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Authors and Affiliations

  1. Washington University in St. Louis, 660 S. Euclid Avenue, St. Louis, MO, 63110, USA

    Rowena Delos Santos

  2. Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Eric D. Langewisch & Douglas J. Norman

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  1. Rowena Delos Santos
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  2. Eric D. Langewisch
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  3. Douglas J. Norman
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Correspondence to Douglas J. Norman .

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Editors and Affiliations

  1. Department of Nephrology, University of Maryland, Baltimore, Maryland, USA

    Matthew R. Weir

  2. Department of Medicine, Section of Nephrology, University of Illinois, Berwyn, Illinois, USA

    Edgar V. Lerma

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Santos, R.D., Langewisch, E.D., Norman, D.J. (2014). Immunological Assessment of the Transplant Patient. In: Weir, M., Lerma, E. (eds) Kidney Transplantation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0342-9_2

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  • DOI: https://doi.org/10.1007/978-1-4939-0342-9_2

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