ABO compatibility and ABO-incompatible transplantation

ABO compatibility refers to matching the ABO blood group of an organ donor and recipient so that the recipient's preformed anti-A and anti-B antibodies do not attack the graft.[1][2] The ABO antigens behave as transplantation antigens because they are expressed not only on red cells but also on vascular endothelium; a recipient with naturally occurring antibody against a donor's blood-group antigen can therefore mount an immediate antibody-mediated attack on the graft vasculature, producing hyperacute or accelerated rejection.[1][3] For this reason, deceased-donor solid-organ allocation is, as a rule, ABO-compatible. ABO-incompatible (ABOi) transplantation is nonetheless performed deliberately in specific settings, most established in living-donor kidney transplantation and in infant heart transplantation, using protocols that lower or circumvent the recipient's anti-donor isoagglutinins.[2][4] ABO matching is assessed alongside HLA-based immunologic risk (see Human leukocyte antigen (HLA) and tissue typing).

The ABO blood group system

The ABO system classifies blood into groups A, B, AB, and O according to which carbohydrate antigens (A, B, both, or neither) are present on cell surfaces.[1] A defining feature is the presence of naturally occurring isoagglutinins: individuals make IgM (and some IgG) antibodies against the A or B antigens they lack, without prior transfusion or transplantation. Thus a group O person has both anti-A and anti-B, a group A person has anti-B, a group B person has anti-A, and a group AB person has neither.[1][2] Because these antibodies are already present, an ABO-incompatible graft can be attacked immediately on reperfusion.[1][3]

In transplantation, compatibility follows the transfusion logic: a group O donor organ can go to any ABO recipient (universal donor), and a group AB recipient can accept an organ of any ABO type (universal recipient).[1][2] Importantly, in deceased-donor kidney allocation this universality is constrained by policy to protect access for group O candidates, who can only receive group O organs and would otherwise be disadvantaged if group O organs were freely given to non-O recipients.[5]

Why ABO matters in transplantation

ABO antigens are expressed on the endothelium lining graft blood vessels.[3] When recipient anti-A or anti-B antibody binds donor endothelium, it activates complement and the coagulation cascade, causing rapid microvascular thrombosis, graft swelling, and ischemic necrosis, the mechanism of hyperacute rejection, which can destroy a graft within minutes to hours.[1][3] ABO incompatibility was historically considered as absolute a barrier as a positive crossmatch (see Transplant rejection).

ABO-incompatible transplantation

Advances in antibody removal and B-cell modulation have made planned ABOi transplantation feasible in selected programs, expanding the living-donor pool.[2][4]

Kidney

ABOi living-donor kidney transplantation is the most established application. Protocols combine pre-transplant antibody removal (plasmapheresis or immunoadsorption to lower the recipient's anti-A/anti-B titer below a program-defined threshold) with B-cell-directed therapy (commonly rituximab, which has largely replaced surgical splenectomy) and maintenance immunosuppression.[4][6] After transplantation, many recipients develop accommodation, a state in which the graft continues to function despite the return of isoagglutinins and the presence of blood-group antigen, for reasons that are incompletely understood.[4] Contemporary series report graft survival approaching that of ABO-compatible living-donor transplants, although with somewhat higher early risks of antibody-mediated rejection, bleeding, and infection.[4][6] Where an incompatible pair prefers to avoid desensitization, kidney paired donation offers an alternative route to a compatible organ.[6]

Heart (infant)

In infant heart transplantation, ABO-incompatible grafting is well established because the isoagglutinin-producing immune system is immature in the first months of life, so young infants have low or absent anti-A/anti-B titers.[7] The landmark work of West and colleagues showed that infants could safely receive ABO-incompatible hearts, and ABOi listing now materially shortens waiting time and reduces waitlist mortality for the youngest candidates, who have the highest death rate while waiting.[7]

Liver

The liver is comparatively resistant to antibody-mediated injury, and ABO-incompatible liver transplantation is performed, chiefly in urgent situations and in young children; in adults it carries increased risks (including antibody-mediated rejection and biliary complications) and typically requires desensitization.[2]

Practical assessment

ABO typing is a routine, rapid serologic test performed on both donor and recipient as part of the pre-transplant evaluation, and ABO verification is a critical patient-safety checkpoint because an inadvertent ABO-incompatible transplant is a serious, potentially fatal error.[1][5] When ABOi transplantation is planned, the recipient's isoagglutinin titer is measured serially before and after transplant to guide antibody-removal therapy and to monitor for rejection.[4] Titer thresholds, desensitization regimens, and program eligibility vary between centers and are individualized clinical decisions.[4][6]

See also

• Human leukocyte antigen (HLA) and tissue typing
• Donor-specific antibodies (DSA)
• Transplant rejection
• Panel-reactive antibody / cPRA and sensitization
• Immunosuppression in transplantation

References

• Dean L. Blood Groups and Red Cell Antigens. Chapter 5: The ABO blood group. NCBI Bookshelf, NBK2267. https://www.ncbi.nlm.nih.gov/books/NBK2267/
• Justiz Vargas AN, et al. Transplantation Immunology. StatPearls. NBK538218. https://www.ncbi.nlm.nih.gov/books/NBK538218/
• Acute Transplantation Rejection. StatPearls. NBK535410. https://www.ncbi.nlm.nih.gov/books/NBK535410/
• Montgomery RA, Locke JE, et al. ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation. 2009;87(8):1246-1255. PMID:19384174. https://pubmed.ncbi.nlm.nih.gov/19384174/
• OPTN. Kidney allocation policy (ABO matching and protections for blood type O candidates). https://optn.transplant.hrsa.gov/policies-bylaws/policies/
• Scurt FG, et al. Clinical outcomes after ABO-incompatible kidney transplantation: a systematic review and meta-analysis. Lancet. 2019;393(10185):2059-2072. PMID:31006573. https://pubmed.ncbi.nlm.nih.gov/31006573/
• West LJ, et al. ABO-incompatible heart transplantation in infants. N Engl J Med. 2001;344(11):793-800. PMID:11248154. https://pubmed.ncbi.nlm.nih.gov/11248154/