What is Human Leukocyte Antigen (HLA) matching and is ABO (Blood Type) compatibility necessary for transplantation?

Understanding HLA Matching and ABO Compatibility in Transplantation

HLA Matching

HLA matching refers to the compatibility between donor and recipient human leukocyte antigens, which is critical for transplant success, with better matching significantly reducing the risk of rejection, graft failure, and mortality. 1

• HLA (Human Leukocyte Antigen) molecules are expressed on almost all nucleated cells and are the major molecules that initiate graft rejection 2
• There are multiple HLA loci that are important in transplantation:
  • Class I: HLA-A, -B, and -C 1, 3
  • Class II: HLA-DR, -DQ, -DP 3, 2
• HLA matching is particularly important for kidney and bone marrow transplantation, where efforts are made to match at HLA-A, -B, and -DR loci 2
• The degree of HLA matching directly impacts transplant outcomes:
  • Each additional HLA mismatch increases mortality risk in a dose-dependent manner 1
  • The impact is greater (10% lower survival per mismatch) in low-risk disease patients compared to high-risk disease patients (5% lower survival per mismatch) 1

Modern Approaches to HLA Matching

• Traditional HLA matching focused on HLA-A, -B, and -DR loci, but newer evidence highlights the importance of HLA-DQ matching 1
• Molecular genotyping provides more accurate HLA typing than serological methods, particularly important for African American patients who have higher rates of serotyping discrepancies (36.3% showed either HLA-A or HLA-B discrepancy) 1
• Eplet-based matching is emerging as a more refined approach:
  • Optimal cutoff for HLA eplet mismatch is <20 total eplet mismatches 4
  • Particularly important to minimize HLA-DQ eplet mismatches to <7 4
• HLA-DQ mismatches are increasingly recognized as critical risk factors:
  • 54-77% of patients with de novo donor-specific antibodies develop antibodies against HLA-DQ 4, 5
  • These antibodies are associated with antibody-mediated rejection, transplant glomerulopathy, and graft loss 5

ABO Compatibility

ABO compatibility does not mean donor and recipient must have the same blood type, but rather that the recipient's antibodies must not react against the donor's blood group antigens. 1

• ABO compatibility follows these general rules:
  • Type O donors can donate to any blood type (universal donor)
  • Type AB recipients can receive from any blood type (universal recipient)
  • Type A donors can donate to type A and AB recipients
  • Type B donors can donate to type B and AB recipients 1
• Standard practice is to transplant ABO blood group donors into identical ABO blood group recipients 1
• Some exceptions exist:
  • Type A2 donors have lower blood group antigen expression and can sometimes donate to type O recipients 1
  • ABO-incompatible transplantation is possible with desensitization protocols but carries higher risks 6

Clinical Implications and Recommendations

• Whenever possible, donors who are high-resolution matched at HLA-A, -B, -C, and -DRB1 should be sought 1
• If a mismatch is unavoidable, a single-locus mismatched donor can be used with acceptable risks 1
• For kidney transplantation:
  • The blood group of the recipient should be compatible with that of the donor 1
  • Donors and recipients should be matched as closely as possible for HLA-A, -B, and -DR antigens 1
  • HLA-A, -B, and -DR antigens should be determined using standard serological and/or molecular procedures 1
  • Molecular genotyping of HLA antigens should be strongly considered for African American renal transplant candidates 1
• More intensive immunosuppression protocols and more frequent monitoring may be necessary when eplet mismatches exceed recommended thresholds 4

Evolving Approaches

• Kidney paired exchange programs help improve outcomes by circumventing HLA or ABO antibody barriers 6
• Desensitization strategies including plasmapheresis and immunoadsorption can facilitate transplantation in HLA-sensitized or ABO-incompatible recipients 6
• High-throughput sequencing and in silico mapping are being used to determine transplant population frequencies and matching probabilities of antibody-binding eplets across HLA genes 7
• Balancing equity of access with optimizing outcomes remains challenging, as strict HLA matching requirements can disadvantage certain ethnic groups 4