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Human Leukocyte Antigens Definition
Human Leukocyte Antigens are unique proteins (antigens) present on every nucleated cell (cell that has a nucleus) in the body. Also called histocompatibility locus antigens, HLAs allow the IMMUNE SYSTEM to identify cells as self (belonging to the body). Genes on CHROMOSOME 6, in a region called the MAJOR HISTOCOMPATIBILITY COMPLEX (MHC), regulate HLAs. Each person has unique HLAs. The nomenclature (naming convention) for HLAs identifies the ALLELE and GENE locus (position on the chromosome), designating the former with a letter and the latter with a number.
HLAs have various immune roles, including identification of self and nonself cells. This function makes HLAs of crucial importance in ORGAN TRANSPLANTATION. Incompatibility in HLAs can result in GRAFT VS. HOST DISEASEand rejection of the transplanted organ. IMMUNOSUPPRESSIVE THERAPY to subdue the IMMUNE RESPONSE in people who have organ transplants in part targets HLAs. Some research suggests that HLAs also may play crucial roles in the development of AUTOIMMUNE DISORDERS such as SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), MULTIPLE SCLEROSIS, and SJÖGREN’S SYNDROME.
Though there are nearly endless configurations of HLAs, there are three broad groups of HLAs: HLA-A, HLA-B, and HLA-DR. Each set of three is called a haplotype. Every person has two specific HLAs from each of the three groups, for a total of two haplotypes (six HLAs). Each parent passes one haplotype to each child. Tissue matching for organ transplantation compares the donor’s six HLAs with the recipient’s six HLAs. The more that match, the more likely the organ transplant will be successful. The fewer that match, the greater the risk that the recipient’s immune system will attack the donor organ.
The other key factor in HLA matching is immune reactivity (ANTIBODY reaction). It is possible to develop antibodies to HLAs that, even with a match, make it almost certain that the recipient will reject the organ. The most common cause for HLA antibodies is exposure to nonself HLA as a result of BLOOD TRANSFUSION. HLA matching is not a component of blood typing. It is possible to have immune reactivity to multiple HLA proteins, which increases the difficulty of locating a good match for organ transplantation. Typically transplant centers like to see a match on four or more of the HLAs. A match of three or fewer strongly suggests the recipient will reject the transplantedorgan.