Editing Histocompatibility (section)

== Role in transplantation ==
[[File:HLA.svg|thumb|HLA genes and their location on chromosome 6]]

After receiving a transplant, the recipient's T cells will become activated by foreign MHC molecules on the donor tissue and trigger the immune system to attack the donated tissue<ref name="Ingulli_2010"/> The more similar HLA alleles are between donor and recipient, the fewer foreign targets exist on the donor tissue for the host immune system to recognize and attack.<ref>{{cite journal | vauthors = Trowsdale J, Knight JC | title = Major histocompatibility complex genomics and human disease | journal = Annual Review of Genomics and Human Genetics | volume = 14 | pages = 301–23 | date = 2013 | pmid = 23875801 | doi = 10.1146/annurev-genom-091212-153455 | pmc=4426292}}</ref> The number and selection of MHC molecules to be considered when determining whether two individuals are histocompatible fluctuates based on application, however matching HLA-A, HLA-B, and HLA-DR has been shown to improve patient outcomes.<ref name="Zachary_2016">{{cite journal | vauthors = Zachary AA, Leffell MS | title = HLA Mismatching Strategies for Solid Organ Transplantation - A Balancing Act| journal = Frontiers in Immunology | volume = 7 | pages = 575 | date = 2016 | pmid = 28003816 | doi = 10.3389/fimmu.2016.00575 | pmc=5141243| doi-access = free}}</ref> Histocompatibility has a measurable effect on whole organ transplantation, increasing life expectancy of both the patient and organ.<ref name="Ingulli_2010" /> HLA similarity is therefore a relevant factor when choosing donors for tissue or organ transplant. This is especially important for pancreas and kidney transplants.

Due to the inherited nature of HLA genes, family members are more likely to be histocompatible. The odds of a sibling having received the same haplotypes from both parents is 25%, while there is a 50% chance that the sibling would share just one haplotype and a 25% chance they would share neither. However, variability due to [[Chromosomal crossover|crossing over]], haplotypes may rearrange between generations and siblings may be intermediate matches.<ref>{{cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK459467/ |title=Major histocompatibility complex: Antigen processing and presentation |last1=Cruz-Tapias |first1=Paola |last2=Castiblanco |first2=John |last3=Anaya |first3=Juan-Manuel | name-list-style=vanc |date=2013-07-18 |publisher=El Rosario University Press}}</ref>

The degree of histocompatibility required is dependent on individual factors, including the type of tissue or organ and the medical condition of the recipient. While whole organ transplants can be successful between unmatched individuals, increased histocompatibility lowers rates of rejection, result in longer lifespans, and overall lower associated hospital costs.<ref>{{cite journal | vauthors = Takemoto S, Port FK, Claas FH, Duquesnoy RJ | title = HLA matching for kidney transplantation | journal = Human Immunology | volume = 65 | issue = 12 | pages = 1489–505 | date = December 2004 | pmid = 15603878 | doi = 10.1016/j.humimm.2004.06.008 }}</ref> The impact of HLA matching differs even among whole organ transplants, with some studies reporting less importance in liver transplants as compared to heart, lung, and other organs.<ref name="Zachary_2016" /> In comparison, [[Hematopoietic stem cell transplantation|hematopoietic stem cell transplants]] are often require higher degrees of matching due to the increased risk of [[graft-versus-host disease]], in which the donor's immune system recognizes the recipient's MHC molecules as foreign and mounts an immune response.<ref>{{cite journal | vauthors = Apperley J, Niederwieser D, Huang XJ, Nagler A, Fuchs E, Szer J, Kodera Y | title = Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States | journal = Biology of Blood and Marrow Transplantation | volume = 22 | issue = 1 | pages = 23–6 | date = January 2016 | pmid = 26551633 | doi = 10.1016/j.bbmt.2015.11.001 | doi-access = free }}</ref> Some transplanted tissue [[Immune privilege|is not exposed to T cells]] that could detect foreign MHC molecules, such as [[Corneal transplant|corneas]], and thus histocompatibility is not a factor in transplantation.<ref>{{Cite book |title=Immune response and the eye: in memoriam J. Wayne Streilein |date=2007 |publisher=Karger |others=Niederkorn, J. Y. (Jerry Y.), 1946-, Kaplan, Henry J., Streilein, J. Wayne. |isbn=9783805581875 |edition= 2nd, rev. |location=Basel |oclc=85243138}}</ref> Individual factors such as age sometimes factors into matching protocol, as the immune response of older transplant patients towards MHC proteins is slower and therefore less compatibility is necessary for positive results.<ref>{{cite journal | vauthors = Dreyer GJ, Hemke AC, Reinders ME, de Fijter JW | title = Transplanting the elderly: Balancing aging with histocompatibility | journal = Transplantation Reviews | volume = 29 | issue = 4 | pages = 205–11 | date = October 2015 | pmid = 26411382 | doi = 10.1016/j.trre.2015.08.003 }}</ref> Post-operative [[immunosuppressant]] therapy is often used to lessen the immune response and prevent tissue rejection by dampening the immune system's response to the foreign HLA molecules,<ref>{{cite journal | vauthors = van Sandwijk MS, Bemelman FJ, Ten Berge IJ | title = Immunosuppressive drugs after solid organ transplantation | journal = The Netherlands Journal of Medicine | volume = 71 | issue = 6 | pages = 281–9 | date = July 2013 | pmid = 23956308 }}</ref> and can increase the likelihood of successful transplantation in non-identical transplant recipients.<ref>{{cite journal | vauthors = Petersdorf EW | title = Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation | journal = F1000Research | volume = 6 | pages = 617 | date = 2017-05-03 | pmid = 28529723 | doi = 10.12688/f1000research.10990.1 | pmc=5419254 | doi-access = free }}</ref>