From the Guidelines
HLA matching is crucial in organ and stem cell transplantation to minimize the risk of graft rejection, graft-versus-host disease (GVHD), and improve patient survival, with a full HLA match (typically 6/6 or 8/8 match) being the ideal scenario, especially for stem cell transplants, as supported by the most recent study 1. The significance of Human Leukocyte Antigen (HLA) matching lies in its ability to reduce the risk of adverse outcomes in transplantation, including increased immunosuppression, pronounced adverse effects, increased comorbidities, reduced quality of life, graft failure, and increased risk of death 1. Key aspects of HLA matching include:
- HLA typing of both donor and recipient
- Comparing HLA-A, HLA-B, and HLA-DR antigens (6/6 match)
- Sometimes including HLA-C for an 8/8 match
- Minimizing mismatches, particularly in the HLA-DQ locus, as mismatches in this locus have been associated with an increased risk of de novo donor-specific antibody (DSA) development and graft rejection 1
- Avoiding nonpermissive HLA-DPB1 mismatches, which have been shown to have an adverse impact on overall survival (OS) 1 The process of HLA matching is complex and involves careful consideration of various factors, including the direction of mismatch, the level of expression of the mismatched HLA molecule, and the presence of donor-specific antibodies (DSAs) 1. In cases where a full HLA match is not possible, partial matches may be acceptable, particularly for solid organ transplants, and the selection of the best partially matched unrelated donor should be based on guidelines that take into account factors such as HLA typing, donor age, and the presence of DSAs 1. Overall, the goal of HLA matching is to find the closest match possible to minimize the risk of adverse outcomes and improve patient survival, with the most recent evidence supporting the importance of minimizing HLA mismatches, particularly in the HLA-DQ locus, to achieve optimal transplant outcomes 1.
From the Research
Significance of HLA Matching
The significance of Human Leukocyte Antigen (HLA) matching can be understood through its benefits in organ transplantation, including:
- Better graft function
- Fewer rejection episodes
- Longer graft survival
- Possibility of reduced immunosuppression 2 HLA matching is critical for the success of organ and hematopoietic stem cell transplantation, and HLA genes and proteins are associated with autoimmunity, immunity to infections, tumor development, and adverse drug reactions (ADR) 3.
HLA Mismatching Strategies
Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches, including:
- What are the least immunogenic mismatches considering the patient's HLA phenotype
- Should repeated mismatches be avoided
- Is the patient sensitized to HLA and, if so, what are the strengths of the patient's antibodies 2 In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable 4.
HLA Epitope Matching
HLA epitope matching theoretically offers a more precise assessment of donor-recipient HLA compatibility and may more effectively prevent sensitization against foreign tissue 5. Epitope matching can help avoid future allosensitization with the development of anti-HLA antibodies and allow selection of a suitable allograft for highly sensitized patients through virtual crossmatch 6. A better understanding of the immunogenicity and structural characteristics of HLA epitopes will guide the consideration of epitope matching as an important parameter for donor selection in kidney transplant in the near future 6.
Impact of HLA Mismatch
The impact of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered 4. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome 4. Increased numbers of HLA allele mismatches are associated with a higher risk of immunological rejection, de novo donor-specific HLA antibody development and graft failure 5.