“When something goes wrong, the immune system knows. It diagnoses the problem and tries to treat it,” Jian Han, MD, PhD, said. “We want to learn what the immune system can teach us about improving our ability to diagnose diseases, evaluate the prognosis of patients and manage their treatment.”
An investigator at the nonprofit HudsonAlpha Institute of Biotechnology in Huntsville, Han is leading the Repertoire 10K project, an international collaborative effort to identify disease-specific T cell and B cell receptor sequences in 10,000 patients who have 100 diseases.
The privately funded project is looking for personal biomarkers in people who have cancer or an autoimmune, inflammatory or infectious disease. Information gathered will provide a reference database for research and for identifying immune diseases with a genetic basis.
“The immune repertoire is the sum of T and B cells in a body at any given moment,” Han said. “It’s like a snapshot of health status and a historical record of immune function. It can also offer a clearer view of an individual’s risk for specific diseases.”
Unlike whole-genome studies that are unable to factor in environmental responses, immune cells are influenced by both genetics and individual response to the environment. Data from the Repertoire 10K project could provide a starting point for better understanding the interaction of genetics and environment in disease.
“We’re two years into the project and it’s going very well,” Han said. “Our teams from the U. S., Europe and Asia have completed sequencing samples from 3,000 people. High throughput sequencing technology is advancing rapidly, so we can do the sequencing faster. The bottleneck is data analysis. The tremendous volume of data in the immune repertoire is highly demanding, and we use a lot of computing power.”
Findings from the study are already yielding intriguing clues related to breast cancer. Han and his team are also developing the D50 test to measure the diversity of a person’s immune repertoire. Much as a white blood cell count signals infection, the D50 offers another window into what has been going on in the body.
“The immune system is very diverse and very smart, but no one’s immune system is perfect,” Han said. “When the immune response is too strong, there is inflammation and autoimmune diseases. If it’s too weak, there’s infection or cancer.”
In choosing which diseases to include among the 100 studied in the project, priority was given to disorders with either high incidence or high mortality rates where diagnosis would significantly improve patient care and make an immediate clinical impact.
“We’ve been working with UAB on specific diseases like Crohn’s and cancer. We’re also looking at disorders linked to immune function such as MS and Parkinson’s,” Han said. “Alabama has high rates of autoimmune diseases, including some of the highest rates of arthritis and lupus in the country. We hope finding personalized biomarkers in the immune system will lead to better and earlier diagnosis and improved treatment.”
In addition to the Repertoire 10K project, HudsonAlpha Institute is involved in several areas of genetics research that are bringing Huntsville recognition as an emerging leader in the field. Rick Myers, PhD, president and director of HudsonAlpha, is continuing work with the Encyclopedia of DNA Elements consortium, an international collaboration of research groups funded by the National Human Genome Research Institute. The goal of ENCODE is to build a comprehensive parts list of functional elements in the human genome.
Scientists at HudsonAlpha are conducting genetic and genomic research into a variety of human diseases, including childhood genetic disorders, major depressive and bipolar disorders, schizophrenia, amyotrophic lateral sclerosis; cancer, Parkinson’s, Alzheimer’s and cardiovascular diseases.
When the Repertoire 10K project is completed a few years from now, it will be another major step forward in understanding how diseases develop, identifying them faster, and finding better ways to treat and perhaps even prevent them.
“The immune repertoire libraries will be totally public open research everyone can use. The data will be free to the research community as a resource they can build on,” Han said.
