KAREN CEROSALETTI, PhD
Member of the Translational Research Program
Benaroya Research Institute
Can we identify T-cell receptor
signatures that track autoimmune
disease type 1 diabetes?
WHAT'S YOUR FOCUS?
We’re researching the autoimmune disease type 1 diabetes to see if we can identify T-cell receptor signatures that track with the disease. Our objective is to determine if these T-cell receptor signatures can predict disease initiation, prior to destruction of the beta cells in the pancreas, when therapies could be implemented to preserve insulin secretion.
Further, if we’re able to identify these signatures as being biomarkers, we could be more effective at monitoring disease progression and response to treatment. These signatures could even be therapeutic targets.
This research project began as a pilot and feasibility study by a consortium—called the Autoimmune Center Consortium—with many investigators, funded by the Juvenile Diabetes Research Foundation (JDRF). The Benaroya Research Institute is the coordinating center for the consortium grant.
We’re also collaborating with Adaptive, which is conducting similar research with a grant from the National Institute of Health (NIH). By combining our resources, we’re able to recruit more subjects and bring in more data. We’re fortunate to be investigating a relatively large group that includes 9 diabetics, 11 controls, 5 at risk individuals.
“The immunoSEQ technology is enabling us to look at the T-cell receptors in T-cells isolated from peripheral blood in great depth and detail.”
HOW HAS IMMUNOSEQ HELPED IN YOUR RESEARCH?
The immunoSEQ technology is enabling us to look at the T-cell receptors in T-cells isolated from peripheral blood in great depth and detail.
In the past, we couldn’t have examined the peripheral T-cell repertoire the same way due to the breadth of its diversity. But immunoSEQ’s high throughput sequencing capability now makes this possible.
Really, we wouldn’t be doing this project if it weren’t for high throughput sequencing technologies like immunoSEQ.
SO WHAT DID YOU THINK?
Adaptive offers a smooth operating procedure. Its system, its platform, and the ability to request different depth levels work well to produce a tremendous amount of data.
The challenge is figuring out how to analyze all the data! And this has been no small task. Unlike many projects, we’re not looking for a particular T-cell receptor that was present before therapy in an individual. We’re trying to determine patterns from the sea of data from many individuals. In this area, my colleagues, Drs. Chester Ni and Damien Chaussabel in the Systems Immunology Program at Benaroya Research Institute have provided valuable input to the analysis and bioinformatics support.
Well, we’re still in the process of analysis. I think the biggest surprise is how complex the analysis is for the T-cell receptor. We are really building from the ground up.
Due to the number of subjects, the range of diversity is quite challenging. As we added more individuals, the diversity is just multiplied, so it is virtually impossible to detect statistical significance at the individual T-cell receptor level.
We are already designing follow-up assays to test for candidate T-cell receptors identified as part of this work in order to validate them as tracking with disease.
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