INNOVATION
HISTOCOMPATIBILITY TESTING FOR THE XENOTRANSPLANT STUDY
The UAB Comprehensive Transplant Institute performs human leukocyte antigen ( HLA ) testing prior to organ transplantation , to help ensure a good match between donor and recipient and reduce the risk of rejection . This testing is carried out by the Institute ’ s state-of-the-art Histocompatibility and Immunogenetics Lab , which plays an important role in the transplant process .
Leading up to UAB ’ s first clinical-grade pig-to-human kidney xenotransplant , the laboratory , under the direction of Vera Hauptfeld- Dolejsek , PhD , developed swine leukocyte antigen ( SLA ) testing protocols for similarly determining how well a pig ’ s organs would match with a particular human recipient . Julie Houp , an associate director in the lab , participated in UAB ’ s groundbreaking xenotransplant study , which explored the science behind SLA testing while evaluating the real-world viability of pig-to-human organ transplants .
The laboratory ’ s research showed that the risk of incompatibility is much lower than with human-to-human transplants , and it also demonstrated that SLA testing is effective in identifying poor matches between species . Next steps include scaling up its SLA testing capability to support the volume that would be needed for a major clinical trial with human recipients and establishing guidelines for post-transplant monitoring .
Although humans are not expected to possess anti-SLA antibodies stemming from prior sensitization events , pre-existing anti-HLA antibodies may cross-react with SLA alleles .
“ In theory , it shouldn ’ t be that way , because most people presumably have not been exposed to SLA , so we would assume that they wouldn ’ t make antibodies and be incompatible ,” Houp says . “ But it turns out that there is a lot of homology between the species , so when they are incompatible with certain HLA , they are incompatible to certain SLA for the same reasons . There is a cross-reaction .”
Despite the progress the laboratory has made with SLA testing , Houp says much work remains to be done .
“ We ’ ve only scratched the surface at this point ,” she says . “ We have to determine exactly what is responsible for that cross-reaction . We know that we can get cross-reactivity , and we can get a positive cross-match in this model , so that ’ s important . We can get a negative cross-match , which is important as well . The fact that we established a positive control tells us that a negative result is meaningful . If all we ever got was negative , then we wouldn ’ t know whether we are detecting something relevant or not .”
INNOVATION
Procured at a pathogen-free facility , the pig kidneys were modified with 10 key gene edits that made them suitable for direct clinical-grade therapeutic use in humans . Serologic compatibility was assessed between the donor pig and the human decedent recipient prior to transplant . The recipient was tested at regular intervals post-transplant for the presence and / or development of HLA-specific antibodies . The gene-modified pigs do not express red blood cell antigens and therefore are “ universal donors ” with respect to human blood type .
“ Obviously we want to be able to adapt this for wider use , and that would include post-transplant monitoring ,” Houp says . “ That really wasn ’ t an issue here , because the decedent recipient was only kept alive for several days post-transplant . Under normal circumstances , the recipient hopefully is going to be alive indefinitely , so we will need a way to monitor for rejection , and that ’ s our next big hurdle .” uabmedicine . org / refertransplant 9