What is Transplant Immunology?
The immune system is designed to protect us from harmful viruses, bacteria and malignant tumors. It does this with the help of human leukocyte antigens (HLA), which are genetic fingerprints that help the body distinguish between its own cells and foreign substances. If the immune system detects small fragments of foreign invaders bound to HLA molecules, it responds by attacking to combat the spread of disease.
Just as the body can launch an immune reaction against infection, it can also recognize foreign HLA molecules on transplanted organs and cells, resulting in an immune attack. These reactions are called graft rejection and are very serious, threatening the transplanted organ or cells and the survival of the patient.
To avoid graft rejection and graft-versus-host disease, it is important to find the most compatible donor for every patient. The University of Chicago Medicine's Transplant Immunology and Immunogenetics Laboratory, under the direction of Susana R. Marino, MD, PhD, diplomate of the American Society for Histocompatibility and Immunogenetics (ABHI), offers complete tissue type (histocompatibility) testing using state-of-the-art technology performed by highly qualified staff. The laboratory performs pre-transplant testing and post-transplant monitoring to support UChicago Medicine's transplant programs.
Patients being considered for transplantation undergo extensive evaluations to assess their HLA type, the presence of existing anti-HLA antibodies and to determine the degree of matching with the transplant donor. After transplant, a variety of tests are performed to monitor immune status of the transplant recipient. In addition, the laboratory performs HLA testing for disease association, drug hypersensitivity and for platelet transfusion support.
The Transplant Immunology and Immunogenetics Laboratory performs pre-transplant testing in three areas:
- HLA typing of patients and potential donors to assess the degree of compatibility between them. The better the match of HLA antigens, the lower the chance for harmful post-transplant immune reactions.
- The second area of testing is for detection and characterization of HLA-specific antibodies that could cause potential complications at the time of transplant.
- The final area of pre-transplant assessment — in particular for solid organ transplant patients — is crossmatch testing, which determines if the patient has HLA antibodies that are specific to a potential donor.
Post-transplant testing services include routine monitoring of patients for early signs of rejection by testing for donor-specific HLA and non-HLA antibodies and providing assistance to physicians with the course of treatment for patients who have had transplants.
In addition to the services described above for transplant patients, HLA testing for the following conditions are performed:
Disease association: Patients are HLA typed to determine if they carry genes that are known to be associated with certain diseases. These tests can help physicians diagnose and determine an appropriate treatment plan for their patients.
Drug hypersensitivity: Several drugs are associated with severe reactions if administered to patients that carry certain HLA genes. HLA typing of patients before the prescription of these drugs helps to prevent these potentially life-threatening reactions.
Platelet transfusion support: Patients with low platelet counts are at risk for serious bleeding complications and are often transfused with platelets from healthy donors. However, patients can sometimes produce antibodies to the HLA molecules expressed on platelets, which reduce the effectiveness of platelet transfusion. HLA typing and antibody detection help physicians choose a platelet donor that will result in increased platelet counts for patients in need.
HLA typing (low- and high-resolution for all the genes listed):
- HLA-A, B, C (class I)
- HLA-DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1 (class II)
HLA typing is performed by the following DNA-based methods:
- Reverse sequence-specific oligonucleotide probe (rSSOP)
- Sanger sequence-based typing (SBT)
- Sequence-specific priming (SSP)
Natural killer cell inhibitory receptors (KIR) typing
HLA antibody detection:
- Class I and class II percent reactive antibody (PRA), an estimation of the percent of donors to which the patient has HLA antibodies
- Class I and class II antibody specificity, which provides the exact HLA antigens to which the patient has HLA antibodies
- Donor specific antibodies, or the detection of antibodies that will recognize the actual donor
HLA antibody detection is performed by the following methods:
- Flow antibody screen
- Luminex-based multiplexed antibody detection of HLA phenotypes
- Luminex-based single-antigen HLA antibody detection
- Complement-fixing antibodies (C1q)
- Flow cytometric crossmatch against B and T cells
- Anti-human-globulin complement-dependent crossmatch (AHG-CDC crossmatch)