Immunogenetics, Transplantation and Crossmatches

Several weeks ago, J.J. Cohen lectured about Immunogenetics and Transplantation. We discussed how outcomes of grafts of living tissues between two individuals are dependent upon whether or not the individuals are histocompatible or histoincompatible. In humans the strongest histocompatibility antigens are called the Human Leukocyte Antigens (HLA). Under current UNOS (United Network of Organ Sharing) listings, not only is the HLA-A, HLA-B and HLA-DR loci of interest for the transplant surgeons, but the DQ locus as well. Under UNOS guidelines, prospective crossmatches are typically run to see the compatibility between a donor and a prospective recipient. I say typically because it is the standard with kidneys (a kidney has a cold ischemia time of about 48 hours) and yet a prospective crossmatch is usually not possible for a heart or lung (in which case the cold ischemia time is much shorter). Needless to say, I am talking about a deceased donor. To run a crossmatch (XM), T and B cells are isolated from the donor (using blood, lymph nodes or spleen) and then incubated with the sera of prospective recipients. If antibody binding to both the T and B cells is seen (measured by flow cytometry as a positive XM), we know there is antibody to the donor’s MHC Class I antigen(s) present. Remember that Class I is on all nucleated cells. If a positive XM is seen with only the B-cells, then we know the recipient has antibody to the donor’s Class II antigen(s). Typically, we can predict in advance the outcome of a XM before the XM is even run because both the donor and recipient have been phenotyped and the recipient has been screened not only for antibody specificity, but levels of antibody at each specificity as well. Transplant surgeons have the task of determining what level (if any) of a positive crossmatch they are willing to accept before going to surgery. Many factors come into play in this decision including their patient’s wait time on the UNOS list, how common their patient’s HLA typing is (the more common, the higher chance of another donor coming up again in the future), the health of their patient and how good of a match the donor is for this patient – just to name a few.