Matching ABO blood types that are determined by the presence of A and B antigens on our cells, is a prerequisite for transplantations to avoid immune rejection of the donor’s organ in the recipient. The need to match these antigens reduces the probability of finding a compatible donor, increasing times on waitlists.
Scientists at the Latner Thoracic Surgery Research Laboratories and UHN’s Ajmera Transplant Centre have used two enzymes to convert lungs from blood group A to O, using a circuit system that perfuses donor lungs with the enzymatic solution outside the body (ex vivo lung perfusion, EVLP).
The investigators show, removing A antigens do not lead to any overt changes in lung health. In a simulation of transplantation, they confirm reduced antibody and complement deposition, suggesting that this protocol may reduce immune responses in vivo.
The work published in the journal Science Translational Medicine on February 16, 2022 (“Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs“), could potentially improve fairness in lung allocation, and reduce wait times for transplantation, decreasing mortality for patients on waitlists. The study was an interdisciplinary effort involving multiple organizations in Canada, including UHN, University of Toronto, University of British Columbia (UBC) and University of Alberta.
“With the current matching system, wait times can be considerably longer for patients who need a transplant depending on their blood type,” says Marcelo Cypel, MD, FRCSC, Surgical Director of the Ajmera Transplant Centre, Thoracic Surgeon at UHN’s Sprott Department of Surgery, Professor in the Department of Surgery at the University of Toronto and the Canada Research Chair in Lung Transplantation.
“Having universal organs means we could eliminate the blood-matching barrier and prioritize patients by medical urgency, saving more lives and wasting less organs,” says Cypel, who is senior author of the study.
Individuals of blood groups A, B, AB and O have antigens A, B, both or none, respectively. Transfusions or transplantations across mismatched blood types can trigger immune rejection, although patients with blood type AB can received blood or organs from all other blood types whereas patients with blood type O can only receive blood or organs from individuals of the same blood group.
Patients with type O wait on average twice as long to receive a lung transplant compared to type A patients, explains Aizhou Wang, PhD, Scientific Associate at Cypel’s lab and first author of the paper.
“This translates into mortality. Patients who are type O and need a lung transplant have a 20% higher risk of dying while waiting for a matched organ to become available,” says Wang. “If you convert all organs to universal type O, you can eliminate that barrier completely.”
In an earlier study, Stephen Withers, PhD, professor of biochemistry at UBC, had identified two enzymes (FpGalNAc deacetylase and FpGalactosaminidase) that when used together effectively convert group A red blood cells to group O. This finding was key in creating the universal blood-type organs in the current study that delivers these enzymes to the lungs via the EVLP circuit.
“This group of enzymes that we found in the human gut can cut sugars from the A and B antigens on red blood cells, converting them into universal type O cells,” said Withers. “This opened a gateway to create universal blood-type organs.”
The EVLP system used in the study in Cypel’s lab, pumps nourishing fluids through organs, enabling them to be warmed to body temperature, so that they can be repaired and improved before transplantation. The authors used human donor lungs that not suitable for transplantation from type A donors for this study. They treated one lung with the enzymatic solution to clear its A antigens, leaving the other lung from the same donor untreated.
The team then tested each lung by adding type O blood that has a high concentration of anti-A antibodies, to the EVLP circuit, to simulate an ABO incompatible transplant. They found, the enzymatically treated lungs with depleted antigen A were well tolerated while the untreated ones showed signs of rejection.
The team is currently working on a proposal for a clinical trial to test the system in patients.