Biomarkers That Indicate Low Immunoreactivity to Organ Transplants

Technology Overview

Dr. Yuk Law

Approximately 9 in 1,000 newborns are diagnosed with a congenital heart condition. The infants and children whose conditions are serious enough to require a heart transplant are special in multiple ways. For instance, many of these young patients are immunologically unique: Their thymus was removed (thymectomy) during a surgical procedure to temporarily repair a heart defect while they wait for a suitable heart donation.

During pediatric heart surgery, surgeons often remove all or part of the thymus, which is a large organ in infants and children that sits over the heart. In addition to providing surgeons with access to the heart for the initial repair procedure and for the future transplant surgery, removing the thymus creates space so that postsurgical swelling does not compress the heart.

The thymus is where T lymphocytes mature, so thymectomy can affect or arrest the development of an important subset of immune cells. This partial immunosuppression at an early age can have a profound impact on the success of a subsequent heart transplant. T lymphocytes are among the cells that attack donor tissue as foreign, so they have a central role in short-term and longer-term organ transplant rejection.

Pediatric cardiologist Yuk Law, MD, studies how to reduce the risk of transplant rejection in children who receive heart transplants. Dr. Law and his team at the Seattle Children’s Hospital Heart Transplant Program are investigating the immune cells of pediatric heart transplant patients, many of whom had a thymectomy at an early age for congenital heart surgery or at the time of heart transplant. In particular, the researchers are learning if thymectomy affects a transplant patient’s risk of developing insidious chronic rejection, which is destruction of the donated tissue over months or years.

Dr. Law’s primary research questions are: Is there a specific immunophenotype — meaning the biomarkers and other features of an individual’s immune cells — that identifies transplant recipients who are free from major adverse immunological events? And is thymectomy early in life an associated factor?

The research team is answering these questions with longitudinal studies of a cohort of more than 100 pediatric heart transplant patients, many of whom had their thymus removed when they were young. The study is documenting the patients’ lymphocyte immunophenotypes. Dr. Law and immunologists at the Heart Transplant Program use multichannel flow cytometry to compare lymphocyte surface markers from patients before and after their heart transplant as signatures of the function of the lymphocytes. Within this cohort, some patients will have had a major immunological adverse event related to the heart transplant and some patients will have never experienced such an event. The study results will help the researchers differentiate each group’s immunophenotype to better understand the immunopathogenesis of graft loss over time.

Dr. Law is interested in industry partnerships to advance the identification of biomarkers and cellular signatures associated with immunoquiescence — the absence of major immunological adverse events — to a transplanted organ. Dr. Law’s goal is to use the immunophenotyping results to design cellular therapies that mimic the immunoresponses of patients who do well after transplants and adjust the responses of patients who show signs of transplant rejection. Dr. Law has extensive experience working with industry partners, including collaborating on clinical trials.

Stage of Development

• Preclinical in vitro
• Translational

Partnering Opportunities

• Collaborative research and development opportunity
• Sponsored research agreement
• Tissue sample access
• Consultation agreement
• Clinical trials

Learn More

• Yuk Ming Law, MD
• Heart Transplant Program

Publications

1. Newland DM, Spencer KL, Do LD … Law YM. Prevalence of iron deficiency and anemia in pediatric heart transplant recipients. Clin Transplant. 2024;38(6):e15367.
2. Newland DM, Rosete BE, Law YM, et al. Assessment of the adverse effects of sirolimus versus everolimus in pediatric heart transplant recipients. Pediatr Transplant. 2023;27(3):e14487.
3. Albers EL, Friedland-Little JM, Hong BJ … Law YM. Human leukocyte antigen eplet mismatching is associated with increased risk of graft loss and rejection after pediatric heart transplant. Pediatr Transplant. 2022;26(1):e14126.
4. Kerr SM, Jorgensen NW, Hong BJ … Law YM, et al. Assessment of rejection risk following subtherapeutic calcineurin inhibitor levels after pediatric heart transplantation. Pediatr Transplant. 2020;24(1):e13616.

Last updated July 2026