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What Exactly Is HLA “Matching”? | Cytologics

Overview

HLA matching refers to the process of comparing the human leukocyte antigen (HLA) types of a donor and a recipient to determine the degree of compatibility between them for organ and tissue transplantation.

HLA are proteins found on the surface of cells that help the immune system recognize “self” from “non-self.”[1] HLA laboratories and clinicians determine histocompatibility between a patient and a donor by analyzing certain HLA genes, usually the 6 antigens at the HLA-A, -B and -DRB1 loci.[2] In general, the more of these HLA genes two people share in common, the better match they are for transplantation.

HLA matching is also important in cell and gene therapies, which involve the use of cells or genetic material to treat diseases. In these therapies, HLA matching is important to prevent immune rejection of the therapy and to ensure that the therapy is effective.

Why is HLA “matching” important?

When a person receives an organ transplant or cell therapy, their immune system may recognize the donor tissue as foreign and attack it, leading to rejection or graft-versus-host disease.[3] HLA matching is important because the more closely matched the donor and recipient are in terms of their HLA types, the less likely the recipient’s immune system is to reject the transplant.

HLA matching is usually performed by analyzing the DNA of the donor and recipient to identify the HLA alleles they possess. A higher degree of HLA matching between the donor and recipient is associated with better transplant outcomes, including reduced risk of rejection and longer graft survival.

How is HLA “matching” performed?

HLA matching is typically performed using molecular techniques that analyze the DNA of the donor and recipient to determine their HLA types. There are several methods used for HLA typing, including:

  • Polymerase chain reaction (PCR) sequencing – PCR is a technique that can amplify a specific segment of DNA, making it easier to analyze. PCR sequencing involves amplifying the DNA segments that encode for HLA molecules, and then sequencing these segments to identify the specific HLA alleles present in the sample.
  • Sequence-specific oligonucleotide probes (SSOP) – This technique involves using short, synthetic DNA probes that are specific to known HLA alleles. These probes are labeled with a fluorescent or radioactive tag, and hybridize to the DNA of the donor and recipient, allowing identification of the HLA alleles present.
  • Sequence-specific primers (SSP) – SSP is similar to SSOP, but instead of using probes, short DNA primers are used to amplify specific regions of the HLA genes. The amplified DNA is then analyzed to determine the specific HLA alleles present.
  • Next-generation sequencing (NGS) – NGS is a newer technique that allows for high-throughput sequencing of DNA samples. NGS can be used to sequence the entire HLA region, providing a detailed profile of the HLA alleles present in the donor and recipient.

After the HLA typing is performed, the donor and recipient’s HLA types are compared to determine the degree of compatibility between them. The National Marrow Donor Program guidelines define a minimum acceptable level of matching as 5 of 6 allele matching for HLA-A, -B, and -DRB1 for unrelated donor transplant requests.[4]

What are the risks and challenges of HLA “matching”?

HLA matching is an important aspect of tissue transplantation and cell therapies, but there are several risks and challenges associated with the process, including:

  • Risk of rejection: Even with good HLA matching, there is still a risk of rejection, as the immune system can still recognize the transplanted organ as foreign.
  • Limited donor pool: Finding a suitable donor can be challenging because not all potential donors will be HLA-compatible with the recipient. The more stringent the matching requirements, the smaller the pool of potential donors.
  • Time-consuming and expensive: HLA typing is a time-consuming and expensive process, which can make it challenging to perform for large numbers of potential donors or recipients.
  • Complex HLA genetics: HLA genes are highly polymorphic, meaning that there are many different HLA alleles present in the human population.[5] This can make it difficult to identify compatible donors, especially for patients who have rare HLA types.
  • Need for immunosuppressive drugs: To prevent rejection, recipients of organ transplants typically need to take immunosuppressive drugs for the rest of their lives. These drugs can have significant side effects and increase the risk of infection and other complications.

Conclusion

Overall, HLA matching is an important component of organ and tissue transplantation and cell therapies, but it is not without risks and challenges. Improvements in HLA typing technology and the development of new immunosuppressive drugs may help to overcome some of these challenges in the future.

At Cytologics, our product portfolio includes immune cells with high resolution HLA-A, HLA-B and HLA-C typing. We understand that HLA information is vital to the outcomes of your experiments. Contact us today to discuss how we can support your research with HLA-typed immune cell products.


References

[1] Nordquist H, Jamil RT. Biochemistry, HLA Antigens. Updated 24 Apr 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546662/

[2] Bray, RA, et al. National Marrow Donor Program HLA Matching Guidelines for Unrelated Adult Donor Hematopoietic Cell Transplants. Transplantation and Cellular Therapy. 2008 Sep. Available from: https://www.astctjournal.org/article/S1083-8791(08)00274-7/fulltext

[3] “Graft-Versus-Host Disease.” Leukemia & Lymphoma Society. Accessed on 31 Dec 2023. Available from: https://www.lls.org/treatment/types-treatment/stem-cell-transplantation/graft-versus-host-disease

[4] Bray, RA and Hurley, C. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 14. 45-53. 10.1016/j.bbmt.2008.06.014. https://www.researchgate.net/publication/23188666_National_Marrow_Donor_Program_HLA_Matching_Guidelines_for_Unrelated_Adult_Donor_Hematopoietic_Cell_Transplants

[5] Jin, P., Wang, E. Polymorphism in clinical immunology – From HLA typing to immunogenetic profiling. J Transl Med 1, 8 (2003). https://doi.org/10.1186/1479-5876-1-8
https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-1-8