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Testing is usually performed only in the setting of a planned transplantation where you are either the intended transplant recipient or a possible donor. Testing identifies which human leukocyte antigen (HLA) genes and antigens you have inherited and detects antibodies to HLA antigens that would cause transplants to be unsuccessful; testing may also be done to identify HLA antigen types in platelet blood donors that match transfusion recipients.
Most often, transplant recipients are tested when it is determined that they need a solid organ or hematopoietic stem cell (HSC) transplant. Prior to transplant, potential donors are tested when they are being evaluated for compatibility with a specific recipient or are signing up with a national donor registry.
Some recipients requiring platelet transfusions do not display a rise in their platelet count because of the presence of HLA antibodies. To improve the platelet response, blood donors of platelets are HLA-antigen-matched to the recipient.
A blood sample drawn from a vein in your arm; sometimes, for HLA typing, a swab from the inside of the cheek (buccal swab)
Human leukocyte antigens (HLA) are specialized proteins present on the surface of all cells in the body except red blood cells. The HLA genes that individuals inherit are responsible for the HLA antigens present on their cells. HLA testing identifies the major HLA antigens that are present on the surface of an individual's cells and the antibodies to HLA antigens as well as the genes that are responsible for HLA antigens, primarily to match transplant donors and recipients.
In humans, the HLA genes are located in region of chromosome 6 called the major histocompatibility complex (MHC). The MHC plays an essential role in the management of the immune system. It helps the body's immune system distinguish which cells are "self" and which are "foreign" or "non-self." Any cells that are recognized as "non-self" can trigger an immune response, including the production of antibodies. HLA antibody testing is performed on transplant recipients to determine if they have antibodies that would target the HLA antigens on the donated organ or tissue. HLA antibody testing is also performed on platelet transfusion recipients to determine if they have any antibodies that would target the donor's platelets and prevent a good response to the transfusion.
For hematopoietic stem cell (HSC) transplant, the HLA genes of the donor and recipient must be the same or match as closely as possible for transplantation to be successful and to lessen the chance of developing graft-versus-host disease (GVHD). (See Common Questions below).
In solid organ transplants, such as kidney, heart, or lung transplants, ABO blood group compatibility is critical. After matching ABO types, it is also beneficial to match the HLA antigens between the donor and recipient. Unlike ABO matching, HLA typing mismatches are less critical as long as the recipient has not developed HLA antibodies directed against donor's antigens. Various drugs may be administered to help suppress the recipient's immune system in order to minimize organ rejection.
Finding a donor who is compatible with an intended recipient may sometimes be difficult. Part of the reason is because each HLA gene can have numerous possible forms or variations (alleles). This characteristic is referred to as polymorphic. In addition, there are more than 200 genes that make up the large HLA gene family located on chromosome 6. Considering the many different possible combinations and numerous types of HLA alleles, it can be a challenge to find a suitable donor, especially if the recipient has pre-formed HLA antibodies.
Nevertheless, HLA genes are located close together and inherited together as groups known as haplotypes; thus, a child inherits one haplotype from each parent. Because of this, there is a greater chance that family members will have the same group of HLA alleles compared to non-related potential donors. Often, a recipient's parents, children, or siblings may serve as the best transplant matches.
Read the article on The Universe of Genetic Testing for more on inheritance and the HLA system.
The primary use for human leukocyte antigen (HLA) testing is to match organ and tissue transplant recipients with compatible donors.
HLA testing also includes screening transplant recipients for the presence of antibodies that might target the donated tissue or organ as part of an immune response.
Different kinds of transplants necessitate different levels of matching between donor and intended recipient. This may determine which HLA tests are performed and which HLA genes are tested for.
There are typically three components of testing used to determine HLA compatibility:
If people want to make themselves available to donate hematopoietic stem cells to anyone who needs it, they can sign up with a national registry such as the United States National Marrow Donor Program (NMDP). HLA testing is performed and test results are kept on file to compare with results from those people who need a donor match.
While the person waiting is for a matching donor to become available, HLA antibody testing may be periodically performed and updated to determine if the person has developed additional HLA antibodies. HLA antibody assessment may also be used post-transplant to determine if the recipient has developed antibodies to the transplanted donor HLA antigens. Antibodies formed post-transplant may increase the risk of graft failure.
Since the MHC system is involved in recognizing "self" and "non-self" antigens, HLA gene testing may be used to aid in the diagnosis certain diseases, such as autoimmune disease. The body can inappropriately mount an immune response against its own self-cells, producing antibodies (autoantibodies). More than 100 diseases have been associated with particular HLA genes, such as ankylosing spondylitis, which is associated with the HLA-B27 allele. HLA typing may also be important in preventing reactions to certain medications as side effects have been noted with certain drugs and specific HLA genotypes. (For more on this, see Common Questions below).
Transplant recipients: HLA gene or antigen and antibody testing is typically performed when it is first determined that a person needs to have a transplant. HLA gene and antigen results do not change unless a person has received a hematopoietic stem cell transplant. However, HLA antibody testing and identification may be done periodically and after events, such as a pregnancy, to see if the potential recipient has developed additional HLA antibodies. HLA antibodies may also be produced in response to a recent blood or platelet transfusion.
Post-transplant, the presence of antibodies to donor antigens, along with other assessments such as a tissue biopsy sample of the transplanted organ, may indicate the recipient is experiencing rejection of the transplanted organ. This information is important for the healthcare practitioner to assess and treat promptly.
Transplant donors: HLA gene or antigen typing is performed for family members when they have volunteered to see if they are a match for a relative who needs a kidney, liver, hematopoietic stem cell, or other type of transplant. Living unrelated persons may also be tested as potential donors, and this is frequently the case for kidney transplants. HLA antigen typing is also performed on unrelated individuals who wish to become a bone marrow donor through the donation registry.
When an organ is from a deceased donor, ABO and HLA antigen testing is performed as quickly as possible to match it to a potential recipient. The amount of time available to ensure the greatest viability of the organ ranges from a few hours (e.g., for heart and lungs, 4 to 6 hours) to no more than 1 to 3 days (e.g., for a kidney, 48 to 72 hours; for a liver, 12 to 24 hours).
Crossmatch testing with the potential donor is performed just prior to an organ transplant to ensure compatibility. In the case of living donor transplantation, the crossmatch compatibility testing is usually performed more than once, when the donor is initially identified and again just before the actual transplant procedure.
Specific HLA genes or antigens are identified during HLA testing to ensure solid organ or hematopoietic stem cell transplant compatibility. The typing result of the recipient is compared to those of the potential donor. Results indicate how many antigens match and how many antigen mismatches are present. "0 mismatches" indicates a high probability that the organ or tissue will not be rejected by the recipient.
The absence of recipient HLA antibodies to the donor HLA antigens is very important. Matching a donor with a recipient who has developed antibodies must be carefully considered because the more HLA antibodies a person has developed, the higher risk for rejection.
An incompatible crossmatch result due to donor specific antibodies is usually interpreted as a high-risk transplant, meaning the recipient is at risk for rejection of the transplant. Graft rejection may or may not be treatable with various immunosuppressant drugs.
HLA testing is performed in laboratories that specialize in histocompatibility and immunogenetics. Many are accredited by the American Society of Histocompatibility & Immunogenetics (ASHI) or the College of American Pathology (CAP). Histocompatibility literally means tissue compatibility and involves testing donors and recipients to see if they are HLA matches. Immunogenetics is the study of the relationships between the immune system, genetics, and disease development.
Historically, HLA testing was used to help identify someone (forensic testing) or to determine if people were related (parentage testing), although now there are other, more specific genetic tests available for these purposes. Other uses include disease-association testing and drug hypersensitivity testing. (See next question)
Some HLA gene alleles are associated with certain diseases and autoimmune disorders. They are not diagnostic of the disorders but can be useful in helping to confirm or exclude a diagnosis. Relationships have also been documented between certain alleles and sensitivities to specific drugs. Genetic factors can change the way a therapeutic dose of medication behaves in one individual as compared to others. Currently, HLA antigen typing can sometimes be used to select the optimal medication, while reducing drug reactions and increasing the effectiveness of the treatment.
Some examples of these associations include:
|Gene/Antigen||Disorders and Associations|
|HLA-B27||Ankylosing spondylitis, Juvenile rheumatoid arthritis, Reactive arthritis|
|HLA-DQ2 and HLA-DQ8||Celiac disease|
No. Although both systems are inherited and are important for tissue compatibility, they are independent of each other. The ABO system is located on chromosome 9 and the HLA system is on chromosome 6.
GVHD is a condition that occurs if HLA matching is not close when a recipient receives a transplant from an unrelated donor. This type of transplant is called allogeneic. While it mostly occurs with hematopoietic stem cell transplants, it may occur with solid organ transplants as well. Immune cells (e.g., T cells) from transplanted donor lymphocytes begin to attack recipient's cells and tissues which look "foreign." Usually in stem cell transplantation, the recipient's bone marrow has been destroyed prior to the transplant. Since the recipient often has a weakened immune system (immunocompromised), the recipient's immune system does not initiate this response.
GVHD can be mild or severe and sometimes can be life-threatening. Symptoms include rash, blisters, diarrhea, and jaundice (yellowing of the skin). It can be acute, occurring within 100 days after the transplant procedure, or chronic, typically developing about 3-6 months post-transplant.
Mild GVHD is a good sign in allogeneic transplants used for cancer treatment. It means the donor’s immune cells are working hard to destroy cancer cells remaining in the recipient (also known as graft-versus-leukemia effect). It has been shown that recipients who have mild GVHD have a lower chance of cancer reoccurrence.
Sources Used in Current Review
2017 review performed by Wyenona Hicks, MS, MT(ASCP)SBB, Dean R. Sylvaria, BS, CHS Supervisor, Histocompatibility Lab Beth Israel Deaconess Medical Center and the Lab Tests Online Editorial Review Board.
Ming Ta Michel Lee, Surakameth Mahasirimongkol, Yanfei Zhang, Wimon Suwankesawong, Usa Chaikledkaew, Cristiana Pavlidis, George P. Patrinos, Wasun Chantratita. Clinical application of pharmacogenomics: The example of HLA-based drug-induced toxicity. Public Health Genomics 2014;17(5-6):248-55.
(April 11, 2017) Human Leukocyte Antigens. NIH National Library of Medicine. Available online at https://ghr.nlm.nih.gov/primer/genefamily/hla. Accessed on 04/12/2017.
(February 2013) Craig M Rive, Jack Bourke, and Elizabeth J Phillips. Testing for Drug Hypersensitivity Syndromes. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626363/. Accessed on 04/12/2017.
(May 2, 2016) Frequently Asked Questions About Pharmacogenomics. NIH National Human Genome Research Institute. Available online at https://www.genome.gov/27530645/faq-about-pharmacogenomics/. Accessed on 04/12/2017.
(2015) Graft-versus-host disease. Be The Match. Available online at https://bethematch.org/for-patients-and-families/life-after-transplant/graft-versus-host-disease--gvhd-/. Accessed on 04/12/2017.
(©2017) Mayo Medical Laboratoryies. Narcolepsy-Associated Antigen, HLA-DQB1 Typing, Blood. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/82026. Accessed June 2017.
(June 17, 2002) Smith S. Immunologic Aspects of Organ Transplantation. Medscape. Available online at http://www.medscape.com/viewarticle/436533_11. Accessed June 2017.
Sources Used in Previous Reviews
(Reviewed 2009 February). HLA gene family. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/geneFamily=hla. Accessed November 2009.
Malhotra, P. et. al. (Updated 2009 July 28). Immunology of Transplant Rejection [On-line information]. Available online at http://emedicine.medscape.com/article/432209-overview. Accessed November 2009.
Delves, P. (Revised 2008 September). Human Leukocyte Antigen (HLA) System. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec13/ch163/ch163c.html#sec13-ch163-ch163c-70. Accessed November 2009.
Cassinotti, A. et. al. (© 2009). HLA and Autoimmune Digestive Disease: A Clinically Oriented Review for Gastroenterologists. Am J Gastroenterol 2009; 104:195–217 [On-line information]. Available online at http://www.nature.com/ajg/journal/v104/n1/full/ajg200810a.html. Accessed November 2009.
Hahn, A. ( © 2008). About Histocompatibility and Immunogenetics. American Society for Histocompatibility and Immunogenetics (ASHI) [On-line information]. PDF available for download at http://www.ashi-hla.org/docs/news/ASHI_Science_fact_sheet_Web.pdf. Accessed November 2009.
Greco, F. (Updated 2009 January 1). Histocompatibility antigen test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm. Accessed November 2009.
Murphey, C. and Forsthuber, T. (2008 July 07). Trends in HLA Antibody Screening and Identification and Their Role in Transplantation. Medscape from Expert Review of Clinical Immunology [On-line information]. Available online at http://www.medscape.com/viewarticle/575925. Accessed November 2009.
Kankonkar (2003 October). HLA – SYSTEM. Bombay Hospital Journal. [On-line information]. Available online at http://www.bhj.org/journal/2003_4504_oct/hla_system_549.htm. Accessed November 2009.
Williams, T. (2001 August). Human Leukocyte Antigen Gene Polymorphism and the Histocompatibility Laboratory. Journal of Molecular Diagnostics, v3(3) [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906958/?tool=pubmed. Accessed November 2009.
(Revised 2009 October). What Is a Blood and Marrow Stem Cell Transplant? National Heart Lung and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/dci/Diseases/bmsct/bmsct_whatis.html. Accessed November 2009.
Smith, S. (2002 June 17). Immunologic Aspects of Organ Transplantation. Medscape from Organ Transplantation: Concepts, Issues, Practice, and Outcomes [On-line information]. Available online at http://www.medscape.com/viewarticle/436533_print. Accessed November 2009.
Waknine, Y. (2007 December 13). FDA Warns of Genetic Link to Carbamazepine Skin Reactions. Medscape Today [On-line information]. Available online at http://www.medscape.com/viewarticle/567436. Accessed November 2009.
Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007 Pp 883-890.
Encyclopedia of Surgery: A Guide for Patients and Caregivers: Human Leukocyte Antigen Test. Available online at http://www.surgeryencyclopedia.com/Fi-La/Human-Leukocyte-Antigen-Test.html. Accessed February 2010.
(June 2, 2004) University of Texas Medical Branch: The Kidney Transplant Process. Available online at http://www.utmb.edu/renaltx/process.htm. Accessed February 2010.
Anne Halpin CHS MSc BSc MLT. Laboratory Scientist, Histocompatibility Laboratory, University of Alberta Hospital.
Greco, F. (Updated 2011 February 2). Histocompatibility antigen test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm. Accessed November 2013.
(© 1996-2013). HLA Matching. Be the Match [On-line information]. Available online at http://bethematch.org/For-Patients-and-Families/Finding-a-donor/HLA-matching/. Accessed November 2013.
Malhotra, P. et. al. (Updated 2013 April 16) Immunology of Transplant Rejection. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/432209-overview#showall. Accessed November 2013.
(© 1995-2013). HLA Class II Molecular Typing Disease Association. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/34990. Accessed November 2013.
(© 1995-2013). HLA Class I Molecular Typing Disease Association. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/89185. Accessed November 2013.
(© 2013). HLA Typing/Matching. UC Davis Transplant Center [On-line information]. Available online at http://www.ucdmc.ucdavis.edu/transplant/learnabout/learn_hla_type_match.html. Accessed November 2013.
Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 561.
McPherson, R. and Pincus, M. (© 2011). Henry's Clinical Diagnosis and Management by Laboratory Methods 22nd Edition: Elsevier Saunders, Philadelphia, PA. Pp 946-947.