Abstract
Celiac disease is a common immune-mediated disease characterized by abnormal T-cell responses to gluten. For many patients, symptoms and intestinal damage can be controlled by a gluten-free diet, but, for some, this approach is not enough, and celiac disease progresses, with serious medical consequences. Multiple therapies are now under development, increasing the need for biomarkers that allow identification of specific patient populations and monitoring of therapeutic activity and durability. The advantage of identifying biomarkers in celiac disease is that the underlying pathways driving disease are well characterized and the histological, cellular, and serological changes with gluten response have been defined in gluten challenge studies. However, there is room for improvement. Biomarkers that measure histological changes require duodenal biopsies and are invasive. Less invasive peripheral blood cell and cytokine biomarkers are transient and dependent upon gluten challenge. Here, we discuss established biomarkers and new approaches for biomarkers that may overcome current limitations.
Highlights
Celiac disease (CeD) is a chronic disease mediated by a destructive immune response triggered by gliadin, a protein found in wheat, rye, and barley
RCD type 1 (RCD1) is similar to active CeD with CD3+ polyclonal T cells comprising the majority of intraepithelial lymphocytes
We describe the context of use and limitations of current biomarkers, and how new biomarkers under development may avoid these limitations and play an important part in the clinical development of new therapies
Summary
Celiac disease (CeD) is a chronic disease mediated by a destructive immune response triggered by gliadin, a protein found in wheat, rye, and barley. Phase I/ II programs include TAK-062 (ClinicalTrials.gov identifier: NCT03701555) and latiglutenase (IMGX003), which degrade ingested gliadin [9]; PRV-015 (AMG 714), a monoclonal antibody that blocks IL-15, a cytokine associated with mucosal damage [10]; and TAK-101, which elicits gliadin-specific immune tolerance. These therapies may target patients who are on a GFD but have ongoing symptoms and/or intestinal damage due to inadvertent gluten exposure. As the number of promising therapies for CeD grows, so does the need to measure therapeutic impact on clinically relevant endpoints and distinguish between different patient populations This could be addressed, at least in part, by thoughtful biomarker selection. We describe the context of use and limitations of current biomarkers, and how new biomarkers under development may avoid these limitations and play an important part in the clinical development of new therapies
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