The Role of SLAs in Xenotransplantation.

Szczegóły
Abstrakt

Tytuł:: The Role of SLAs in Xenotransplantation.
Autorzy:: Ladowski JM; Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.
Hara H
Cooper DKC
Źródło:: Transplantation [Transplantation] 2021 Feb 01; Vol. 105 (2), pp. 300-307.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't; Review
Język:: English
Imprint Name(s):: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Williams & Wilkins.
MeSH Terms:: Transplantation, Heterologous*/adverse effects
Antibodies, Heterophile/*blood
Antigens, Heterophile/*immunology
Graft Rejection/*immunology
Histocompatibility Antigens Class I/*immunology
Sus scrofa/*immunology
Animals ; Animals, Genetically Modified ; Antibody Specificity ; Antigens, Heterophile/genetics ; Graft Rejection/blood ; Graft Rejection/prevention & control ; Graft Survival ; Histocompatibility Antigens Class I/genetics ; Humans ; Species Specificity ; Sus scrofa/genetics ; Transplantation Tolerance
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Substance Nomenclature:: 0 (Antibodies, Heterophile)
0 (Antigens, Heterophile)
0 (Histocompatibility Antigens Class I)
0 (swine leukocyte antigen)
Entry Date(s):: Date Created: 20200521 Date Completed: 20210208 Latest Revision: 20231002
Update Code:: 20240105
DOI:: 10.1097/TP.0000000000003303
PMID:: 32433239
: Czasopismo naukowe

Advances in genetic engineering, particularly CRISPR/Cas9, have resulted in the development of a triple glycan-knockout (TKO) pig. There is minimal human antipig antibody binding to TKO pig cells. The TKO background has decreased antibody binding to a sufficiently low level that any additional xenoantigens expressed on the cells can now be more easily detected. One of these xenoantigens is the swine major histocompatibility complex, termed swine leukocyte antigens (SLA). SLA are the homolog to HLAs, a protein complex expressed on human tissue capable of stimulating the development of new antibodies in allotransplantation. These antibodies can result in graft failure through hyperacute, acute, or chronic rejection. Our knowledge of SLA, particularly in the last 5 years, has grown considerably. The presence, cause, and methods to detect anti-SLA antibodies will need to be carefully considered for the first clinical trial of xenotransplantation. The focus of this review is to summarize the role of SLA in xenotransplantation and consider whether it will prove to be a major barrier. Techniques are now available to mutate target SLA amino acids to ensure that cross-reactive anti-HLA antibodies no longer bind to SLA on the cells of the organ-source pigs. While deletion of SLA expression is possible, it would render the pig at risk for infectious complications. The ideal organ-source pig for HLA highly sensitized recipients may therefore be 1 with site-specific mutations to eliminate cross-reactive binding.
Competing Interests: The authors declare no conflicts of interest.
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