A new clinical trial at Seattle Children’s Hospital aims to provide doctors with information about how inflammatory bowel disease (IBD) develops in children. The goal is to find strategies for clinicians to personalize treatments.
The PREDICT (Precision Diagnostics in Inflammatory Bowel Disease, Cellular Therapy and Transplantation) study will employ next-generation sequencing and gene expression analyses to better understand how the immune system drives both pediatric IBD and graft-versus-host disease (GVHD) in children with bone marrow transplants (BMT).
BMT replace damaged or destroyed bone marrow with healthy bone marrow stem cells, and is used to treat a range of pediatric conditions. GVHD is a medical complication following transplanted tissue from a genetically different person. GVHD, commonly associated with bone marrow tranplants, occurs when T-cells (a subset of immune cells) of newly transplanted bone marrow begin to attack a patient’s tissues, including tissues of the gastrointestinal tract, which can be difficult to overcome.
In patients with IBD, a similar disease process is observed where T-cells and other components of the immune system react abnormally over time, causing chronic inflammation in the gastrointestinal tract. However, immunosuppressive therapies have often failed in managing diseases like IBD and GVHD.
The trial will also include children who have had bone marrow transplants to identify the immunologic changes that occur when a patient develops GVHD.
“PREDICT seeks to change the paradigm of treatment by first changing the paradigm of diagnosis,” Leslie Kean, associate director of the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute, said in a news release.
“By gaining foundational molecular diagnostic knowledge about a patient’s T cells, we hope to ultimately discover better treatment approaches for IBD and GVHD,” added Kean, also the trial’s principle investigator who leads a lab focused on T-cell immunology.
The research team will perform TCR sequencing and gene expression analysis on tissue samples from 100 IBD and 250 BMT patients. The results will help researchers identify the molecular pathways that are active within a patient’s T-cells, with the aim of developing therapeutics that target these pathways.
Adaptive Biotechnologies’ immunoSEQ platform will be used to perform the high-throughput T-cell receptor (TCR) sequencing and the subsequent analyses. The single-cell gene expression analysis will be performed using 10x Genomics’ Chromium Single Cell 3′ Solution, which will enable gene expression patterns to be identified in patients’ T-cells.
“IBD and GVHD have a lot more in common than meets the eye when it comes to the underlying immune response they trigger,” Kean said. “PREDICT aims to bridge IBD and GVHD, shedding new light on the immunologic similarities they share and identifying the molecular causes of each patient’s disease. This will create a unique opportunity to make significant headway in the treatment of both diseases, with the focus on each child and their unique disease signature.”