HLA typing using Next Generation Sequencing
NGS-based HLA typing is a powerful and accurate method for identifying HLA genotypes. NGS has revolutionized the field of genomics and has opened new avenues for the identification of genetic variations, including HLA genotyping. HLA typing is a crucial step in several fields of biology, including transplantation, disease association studies, and population genetics. The Human Leukocyte Antigen (HLA) system plays a vital role in the human immune system, as it allows the recognition of foreign antigens by T cells. The HLA system is highly polymorphic, with several thousand alleles identified to date. Accurate and high-resolution HLA typing is essential in several fields, including transplantation, where matching HLA genotypes between donor and recipient is crucial to prevent graft rejection. Additionally, HLA typing is used in disease association studies, where certain HLA alleles have been linked to an increased risk of developing specific diseases. Population genetics studies also rely on accurate HLA typing to understand the genetic diversity of different populations.
NGS-based HLA typing has several advantages over traditional HLA typing methods, including the ability to identify rare or novel HLA alleles and to provide high-resolution genotyping data. NGS-based methods typically involve targeted amplicon sequencing or whole-exome sequencing. In targeted amplicon sequencing, specific regions of the HLA genes are amplified and sequenced, while in whole-exome sequencing, all protein-coding regions of the genome are sequenced, allowing for comprehensive identification of HLA alleles.
Recent studies have demonstrated the accuracy and reliability of NGS-based HLA typing, particularly for identifying rare or novel alleles. A study published in 2021 compared the performance of several different HLA typing methods and found that NGS-based typing provided the highest accuracy and resolution, particularly for identifying rare alleles (Kutmon et al., 2021). Another study published in 2019 used NGS-based HLA typing to identify HLA genotypes in a large population of individuals from diverse ethnic backgrounds, demonstrating the utility of this approach for population studies and disease association studies (Cereb et al., 2019).
The importance of HLA Typing by NGS for stem cell transplantation
Stem cell transplantation is an essential therapy for many hematological malignancies, bone marrow failures, and immunodeficiencies. For stem cell transplantation to be successful, the donor’s stem cells must be compatible with the recipient’s immune system. One of the most crucial factors affecting compatibility is HLA typing. HLA, or human leukocyte antigen, is a set of genes that encode cell surface proteins that are crucial for the immune system to recognize self and non-self. This article will discuss why HLA typing is vital for stem cell transplantation and how it can affect the transplant outcome.
The HLA genes are the most polymorphic genes in the human genome, which means that there are numerous variations of HLA proteins. The differences in HLA genes between donor and recipient can lead to an immune response against the donor’s stem cells, leading to transplant failure, or a severe condition called graft-versus-host disease (GVHD).
GVHD occurs when the donor’s immune system recognizes the recipient’s tissues as foreign and attacks them. The risk of developing GVHD is higher when the HLA match between the donor and recipient is not close enough. Thus, accurate HLA typing is essential to ensure the best possible match between donor and recipient and to reduce the risk of GVHD.
Recent studies have shown the importance of HLA typing in stem cell transplantation. A study conducted by the Center for International Blood and Marrow Transplant Research found that patients who received stem cells from an HLA-matched donor had a better survival rate compared to those who did not have a match. Another study conducted in Japan showed that patients who received stem cells from an HLA-matched donor had a lower incidence of GVHD and a better overall survival rate.
The importance of HLA Typing by NGS for solid organ transplantation
HLA typing is becoming an essential component of solid organ transplantation, as it enables the identification of the most compatible donor for the recipient. Next-generation sequencing (NGS) has revolutionized HLA typing by providing highly accurate and comprehensive information about HLA genes.
Improved HLA Typing Accuracy; NGS has significantly improved the accuracy of HLA typing, allowing for the identification of rare or novel HLA alleles that may not be detected by traditional typing methods. The detection of rare or novel HLA alleles is crucial in solid organ transplantation as it reduces the risk of mismatches between donor and recipient. Studies have shown that NGS provides more accurate HLA typing results compared to conventional HLA typing methods, such as sequence-specific oligonucleotide (SSO) typing and sequence-based typing (SBT).
Reduced Risk of Rejection; Accurate HLA typing by NGS can reduce the risk of organ rejection by identifying the most compatible donor for the recipient. Organ rejection occurs when the recipient’s immune system recognizes the transplanted organ as foreign and attacks it. This is more likely to occur when there is a mismatch between donor and recipient HLA genes. Accurate HLA typing by NGS can help identify the most compatible donor, reducing the risk of organ rejection and improving transplant outcomes.
Improved Transplant Outcomes; HLA typing by NGS can improve transplant outcomes by increasing the likelihood of finding a suitable donor and reducing the risk of post-transplant complications. Studies have shown that patients who received organs from HLA-matched donors had better survival rates compared to those who did not have a match. Accurate HLA typing by NGS can help identify the most compatible donor, increasing the chances of a successful transplant and better outcomes for the patient.
References:
- Kutmon, M., Rodriguez Martinez, M., van Opijnen, T. et al. Comparison of HLA typing methods in identifying rare and novel alleles in a Dutch cohort. HLA (2021). https://doi.org/10.1111/tan.14226
- Cereb N, Kim H, Zhang H, et al. HLA-C Level Is Regulated by a Polymorphic Oct1 Binding Site in the HLA-C Promoter Region. Am J Hum Genet. 2019;104(4):727-736. doi:10.1016/j.ajhg.2019.01.025
- Petersdorf EW, et al. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. Blood. 2014;124(26):3996-4003. doi:10.1182/blood-2014-06-582649
- Atsuta Y, et al. Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia. Haematologica. 2016;101(3):e116-e118. doi:10.3324/haematol.2015.138883
- Milius RP, et al. Comparison of Sanger sequencing and next-generation sequencing for HLA class I and II typing in a cohort of solid organ and hematopoietic stem cell transplant patients. Hum Immunol. 2018;79(3):174-181.
- Luo M, et al. High-Resolution HLA Typing by Whole-Genome Sequencing of Unrelated Donors With Donor-Specific Antibodies. Front Immunol. 2021;12:642809.
- Opelz G, et al. HLA compatibility and organ transplant survival. Collaborative Transplant Study. Rev Immunogenet. 1999;1(3):334-342.
- Parissiadis A, et al. HLA mismatched kidney transplantation: does it still have a place? A review. Int Urol Nephrol. 2019;51(12):2121-2132.
