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Transplant Medicine
The Major Histocompatibility Complex (MHC) contains over 128 functional genes. This is the densest part of the human genome and is responsible for most autoimmune diseases. This region also determines vaccine responsiveness, adverse drug reactions, disease progression and transplant rejection. The MHC genes are multigenic with a high degree of allelic polymorphism. There are over 7,500 different alleles and over 5,458 expressed MHC antigens currently known. (DeFranco, Locksley & Robertson, 2007). Genomic evolution and HLA screening have been extremely profitable to Transplant Medicine.
A brief analysis of MHC variability reveals two classes of antigens belonging to this complex; class I (A, B, and C) and II (DR, DQ, and DP). Both classes of molecules are expressed in a co-dominant fashion. These molecules are designed to recognize antigens that are foreign to the body and present them to the T cells. (Janeway, Travers & Walport, 2001)
The co-dominant mode of inheritance of MHC genes assures that each individual will have a distinct antigen on their cell surface. This forms the basis of graft rejection. Once a foreign antigen enters the human body, activation, proliferation and differentiation of lymphocytes into effector cells continues until the foreign antigen is eliminated, after which the immune system returns to its quiescent state and an immunologic memory is generated. (Janeway, Travers & Walport, 2001)
Tissue typing to match HLA antigens is an important step before transplantation. In general, the larger the number of matched MHC alleles between the donor and the recipient, greater are the chances of graft survival. However, routine HLA typing focuses only on HLA-A,...
(Janeway, Travers & Walport, 2001)
The extreme polymorphism of the MHC genes poses several challenges in recognizing the perfect donor, thus complicating HLA typing. The HLA nomenclature differs with the type of typing method used. Refinement of the serological typing of HLA antigens through the years has led to the identification of additional gene loci, which were previously thought to yield one antigen. For example, the B. 60 and B. 61 antigen were previously thought to be one antigen, the B. 40, based on their common ability to bind to a shared public epitope. Moreover, serology does not recognize heterogeneity of HLA antigens, as confirmed by DNA sequencing. Thus serological nomenclature is not representative of the true heterogeneity of the HLA system. HLA typing through this method may lead to a greater risk of graft rejection. (Badders, Houp, Sholander, Leffell & Zachary, 2010)
Further more, three different nomenclatures exist for defining HLA antigens. It is important to be able to appreciate the differences of each molecular typing nomenclature and to know which system is being used in the laboratory. Failure to do so may result in missed recognition of a donor specific antibody. (Badders et al., 2010)
Apart from the likelihood of graft rejection, recipients are faced with several challenges, such as prolonged waiting times and donor shortage, especially for sensitized individuals since they have additional immunological barriers. From 2000-2008, a total of 243,662 candidates were on the waiting list for kidney transplantation, with only 62,622 available donors in the United…
REFERENCES:
Appel J.Z., Hartwig M.G., Cantu E., Palmer S.M., Reinsmoen N.L., Davis R.D. (2006). Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies.Transplantation 81(7),1049-1057.
Badders J.L., Houp J.A., Sholander J.T., Leffell M.S., Zachary A.A. (2010). Considerations in interpreting solid phase antibody data. Hum Immunol 71(1),S18.
DeFranco, A.L., Locksley, R.M., & Robertson, M. (2007). Immunity: The immune response in infectious and inflammatory disease. (1st ed.). United Kingdom: Oxford University Press. Retrieved from http://www.biomedcentral.com/content/pdf/nsp-mhcpolymorphism.pdf
Janeway, C.J., Travers, P., & Walport, M. (2001).Immunobiology: The immune system in health and disease.. (5th ed.). New York: Garland Science. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK27163/
Reinsmoen, N., Lai, C., Vo, A., & Jordan, S.C. (2012, October 5). Evolving paradigms for desensitization in managing broadly hla sensitized transplant candidates. Retrieved from http://www.discoverymedicine.com/Nancy-Reinsmoen/2012/04/17/evolving-paradigms-for-desensitization-in-managing-broadly-hla-sensitized-transplant-candidates/
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