immunology allergic disorders
Overview of Transplantation
Pretransplantation Screening
Before the risk and expense of transplantation are undertaken and scarce donor organs are committed, medical teams screen potential recipients for medical and nonmedical factors that may affect the likelihood of success. Donors undergo medical screening, psychological screening, and laboratory studies, including tests to evaluate risk of infection. In pretransplantation screening,recipients and donorsare tested for Human Leukocyte Antigen (HLA) System (HLAs; also called the major histocompatibility complex [MHC]) ABO antigens Recipientsare tested for Presensitization to donor antigens HLA tissue typingis most important for the following: Kidney Transplantation None The most common types of Hematopoietic Stem Cell Transplantation None Transplantation of the following typically occurs urgently, often before HLA tissue typing can be completed, so the role of matching for these organs is less well-established: Heart Transplantation None Liver Transplantation None Pancreas Transplantation None Lung and Heart-Lung Transplantation None HLA tissue typing of peripheral blood or lymph node lymphocytes is used to match the most important known determinants of histocompatibility in the donor and recipient. More than 1250 alleles determine 6 HLA antigens (HLA-A, -B, -C, -DP, -DQ, -DR), so matching is a challenge; eg, in the US, only 2 of 6 antigens on average are matched in kidney donors and recipients. Matching of as many HLA antigens as possible significantly improves functional survival of grafts from living related kidney and hematopoietic stem cell donors; HLA matching of grafts from unrelated donors also improves survival, although much less so because of multiple undetected histocompatibility differences. Better immunosuppressive therapy has expanded eligibility for transplantation; HLA mismatches do not automatically disqualify patients for transplantation because immunosuppressive therapy has become more effective. ABO compatibility and HLA compatibility are important for graft survival. ABO mismatches can precipitate hyperacute rejection of vascularized grafts (eg, kidney, heart), which have ABO antigens on the endothelial surfaces. Presensitization to HLA and ABO antigens results from prior blood transfusions, transplantations, or pregnancies and can be detected with serologic tests or, more commonly, with a lymphocytotoxic test using the recipient’s serum and donor’s lymphocytes in the presence of complement. A positive cross-match indicates that the recipient’s serum contains antibodies directed against ABO or class I HLA antigens in the donor; it is an absolute contraindication to transplantation, except possibly in infants (up to age 14 months) who have not yet produced isohemagglutinins. High-dose IV immune globulin and Plasma exchange have been used to suppress HLA antibodies and facilitate transplantation when a more compatible graft is not available. Costs are high, but midterm outcomes are encouraging and appear similar to those in unsensitized patients. Even a negative cross-match does not guarantee safety; when ABO antigens are compatible but not identical (eg, donor O and recipient A, B, or AB), hemolysis is a potential complication due to antibody production by transplanted (passenger) donor lymphocytes. Although matching for HLA and ABO antigens generally improves graft survival, patients who are not White are disadvantaged because Organ donation is less common among people who are not White, and, thus, the number of potential donors who are not White is limited. End-stage renal disease is more common among people of African ancestry, and, thus, the need for organs is greater. Patients who are not White may have HLA polymorphisms that are different from those of donors who are White, a higher rate of presensitization to HLA antigens, and a higher incidence of blood types O and B. Donor and recipient exposure to common infectious pathogens and active as well as latent infections must be detected before transplantation to minimize risk of transmitting infection from the donor and risk of worsening or reactivating existing infection in the recipient (due to use of immunosuppressants). This screening usually includes the history and tests for Cytomegalovirus (CMV) Epstein-Barr virus Hepatitis B virus Hepatitis C viruses Herpes simplex virus (HSV) HIV Mycobacterium tuberculosis Varicella-zoster virus West Nile virus, if exposure is suspected Positive findings may require pre- or posttransplantation antiviral treatment (eg, for Cytomegalovirus (CMV) Infection or Absolute contraindicationsto transplantation include the following: Clinically active infection, except possibly infection in the recipient if it is confined to the organ being replaced (eg, liver abscesses) Cancer (except hepatocellular carcinoma confined to the liver, non-melanoma skin cancers, and certain neuroendocrine tumors) A positive cross-match identified by lymphocytotoxic testing Relative contraindicationsinclude the following: Age > 70 Poor functional or nutritional status (including severe obesity) HIV infection Multiorgan insufficiency Psychologic and social factors also play an important role in success of transplantation. For example, people with a substance use disorder s or those who are psychologically unstable are less likely to firmly adhere to the necessary lifelong regimen of treatments and follow-up visits. Eligibility decisions for patients with relative contraindications differ by medical center. HIV infection is no longer considered an absolute contraindication because antivirals and immunosuppressants are usually well-tolerated by and effective in transplant recipients who require them. 