A new study published in Nature Biomedical Engineeringreports development of a chemiluminescence-based stool assay designed to measure granzyme A (GzmA) enzyme activity as a potential biomarker for monitoring inflammatory bowel disease (IBD). The goal is to provide a noninvasive test that reflects immune activity in the gut, with a focus on T cell–associated inflammation.
IBD diagnosis and assessment still rely heavily on endoscopy and histopathology, supported by laboratory testing such as C-reactive protein and fecal calprotectin. While fecal calprotectin is widely used for monitoring, it primarily reflects neutrophil-driven inflammation and may not capture all inflammatory patterns seen in ulcerative colitis and Crohn’s disease.
In this study, researchers reported increased GzmA in inflamed intestinal tissue and showed that CD8-positive T cells can release active GzmA. The authors also linked GzmA activity to induction of interleukin 8 (IL-8), supporting a role in pro-inflammatory signaling.
To translate these findings into a diagnostic tool, the team developed a chemiluminescence assay to detect active GzmA in stool samples. Instead of measuring protein concentration, the assay detects enzyme activity, producing a light-based signal when GzmA is present and active. This activity-based design is intended to provide a more functional readout of inflammatory processes.
The investigators evaluated the assay using stool samples from about 150 participants, including patients with IBD and healthy controls. Stool GzmA activity was higher in individuals with intestinal inflammation and helped distinguish IBD from controls. The authors suggest the assay could support monitoring by reflecting disease biology related to T cell activity.
This research highlights that activity-based stool biomarkers may eventually complement existing tests. A marker linked to T cell–associated inflammation could be useful in cases where symptoms, endoscopic findings, and calprotectin results do not align. However, the authors note that this remains a research-stage assay and does not replace histologic evaluation, which is still central to diagnosis and disease assessment.
Further validation will be needed to confirm performance across different IBD phenotypes, treatment settings, and real-world preanalytical conditions before clinical adoption.
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