Pacific Biosciences of California Inc, Menlo Park, Calif, has announced publication of the results of a retrospective study conducted by scientists at the Anthony Nolan Research Institute in the United Kingdom. The study demonstrated that ultrahigh-resolution HLA typing performed with PacBio sequencing technology identified stronger matches associated with improved survival rates among patients who received hematopoietic cell transplants.1
Figure 1. The study conducted by the Anthony Nolan Research Institute used the PacBio RS II sequencer, an earlier generation of PacBio’s sequencing instrumentation based on the company’s single molecule, real-time (SMRT) sequencing technology.
HLA typing involves analysis of the genes found in the human leukocyte antigen region of the human genome. For stem cell transplants, HLA typing is used to find the best donor-recipient match for the strongest chance of a positive outcome for transplant patients. HLA genes are highly polymorphic and complex, making them very difficult to resolve fully with conventional technologies. They are also known to be important in immune-related diseases and drug hypersensitivity.
The Anthony Nolan Research Institute maintains the world’s oldest stem cell registry, and has implemented single molecule, real-time (SMRT) sequencing from PacBio to fully phase and characterize HLA genes with high accuracy. In their retrospective study, institute scientists aimed to determine whether high-resolution HLA typing enabled by SMRT sequencing would have made a difference for previously matched donors and recipients.
Figure 2. Launched in April 2019, the Sequel II is PacBio’s latest sequencing platform based on the company’s SMRT technology.
The researchers analyzed 891 donor-recipient pairs, all of which had originally been considered a perfect match (a 12/12 score for all six HLA genes). SMRT sequencing revealed that 29.1% of those matches were not actually perfect, and identified previously undetected variations in nearly a quarter of the pairs.
The patients whose 12/12 matches were confirmed by SMRT sequencing had a significantly improved 5-year overall survival rate of 54.8% compared to the rate of 30.1% for patients found to have previously undetected variations. Perfectly matched patients were also less likely to die of other transplant-related complications in the 12 months after transplant, and significantly less likely to develop acute graft-versus-host disease.
Neema Mayor, PhD, Anthony Nolan Research Institute.
The study highlights the importance of sequencing through previously uncharacterized regions of the traditional HLA genes, showing that polymorphisms in these regions affect patient overall survival.
“We are very excited about this breakthrough, which has told us more than we have ever known about how to match patients and donors,” says Neema Mayor, PhD, head of immunogenetics research at the Anthony Nolan Research Institute. “We believe that HLA matching at ultrahigh resolution could ultimately enable us to further minimize the risk of complications such as graft-versus-host disease and, consequently, the risk of mortality—potentially saving more lives in the future.”
Jonas Korlach, PhD, Pacific Biosciences.
“We congratulate the Anthony Nolan research team for their commitment to continually pushing forward to develop better methods of investigating molecular differences that can influence the outcomes of stem cell transplantation,” says Jonas Korlach, PhD, chief scientific officer at PacBio. “These results offer additional evidence that using SMRT sequencing to characterize polymorphisms in HLA genes outside of the protein binding regions is critical for strengthening causality association studies.”
For further information, visit Pacific Biosciences.
Reference
- Mayor NP, Hayhurst JD, Turner TR, et al. Recipients receiving better HLA-matched hematopoietic cell transplantation grafts, uncovered by a novel HLA typing method, have superior survival: a retrospective study. Biol Blood Marrow Transplant. 2019; 25(3):443–450; doi:10.1016/j.bbmt.2018.12.768.
