Advancing Noninvasive Diagnostics for Inflammatory Bowel Disease, With Jamie Scott, PhD

Despite its central role in inflammatory bowel disease (IBD) pathogenesis, clinicians have historically lacked a way to directly monitor T cell–driven immune activity, instead relying heavily on endoscopy, histology, and nonspecific inflammatory markers.

A novel GzmA activity-based optical assay developed by a team of University of Edinburgh researchers may have the potential to address this gap, accelerating the design of new biomedical approaches to enhance precision medicine in IBD. Their research offers the first non-invasive chemiluminescence assay measuring extracellular active GzmA in stool supernatants from human IBD patients, built using a combination of functional, chemical, and imaging assays in human cells and gut tissue biopsies from IBD patients.

“In the diagnosis and monitoring of IBD patients, there are a number of gaps,” Jamie Scott, PhD, an EiC senior chemist at the University of Edinburgh, told HCPLive. If we focus on the gold standard, colonoscopy, we know that that is a particularly brutal way to assess patients. It's not pleasant, it's time consuming for healthcare systems, and depending on the area of the colon that's sampled, you may get results which do not reflect the true state of the immune system in the gut.”

With these shortcomings in mind, Scott points to the need for the development of noninvasive IBD technologies. By identifying a mechanistic, noninvasive biomarker that reflects adaptive immune activation in the gut, he says his team is hopeful that they have developed a tool that will more easily monitor and diagnose people with IBD.

In the research, investigators observed higher levels of GzmA in patients with active ulcerative colitis (UC) or active Crohn’s disease (CD) in inflamed tissues compared to non-inflamed regions from the same individuals. Because this enzyme is primarily released by CD8+ T cells to induce the secretion of the neutrophil chemoattractant IL-8 by monocytes, its active form serves as an indicator of T cell-mediated inflammation.

Investigators designed a GzmA activity-based chemiluminescence assay for testing clinical biosamples from IBD patients. To do this, they synthesized GzmA-CL as an GzmA-selective activatable chemiluminescent reporter with exceptional reactivity and kcat/KM values around 107 M-1 s-1. They then integrated both GzmA-CL and GzmA-INH into a 96-well plate assay to quantify the chemiluminescence readouts of multiple biosamples and examined stool supernatants from a cohort of IBD patients, including UC and CD patients as well as healthy controls.

Results revealed high levels of active GzmA in IBD patients, corroborating its role in gut inflammation, particularly in patients with highly active disease. While all healthy control samples displayed fecal calprotectin levels under the 50 mg kg-1 threshold, 38% of IBD patients displayed scores in the 50-200 mg kg-1 undefined region.

Of note, the combined analysis of active GzmA from T cells (adaptive) and fecal calprotectin from neutrophils (innate) enhanced monitoring of disease activity in IBD patients (95%) when compared to using fecal calprotectin scores alone (62% range).

“In order to move this technology further along the pipeline to commercialization, there would need to be some discussions with clinicians about what they want,” Scott explained, noting inherent limitations to the technology in its current form as well as the need for a powered statistical study on clinical samples to validate the findings from this pilot study.

Editors’ Note: The University of Edinburgh has filed a patent covering methods for granzyme detection, in which Scott is a named inventor.

References

1. Scott JI, Cheng Z, Thompson EJ, et al. A chemiluminescence assay targeting granzyme A activity for monitoring inflammatory bowel disease. Nat. Biomed. Eng (2026). https://doi.org/10.1038/s41551-025-01588-1

2. University of Edinburgh. New test could help pinpoint IBD diagnosis, study finds. January 13, 2026. Accessed January 14, 2026. https://www.eurekalert.org/news-releases/1112281