Biopsy-Free Diagnosis and the Evolving Perspective on Coeliac Disease

In September 2025, the European Society for the Study of Coeliac Disease (ESsCD) published an update to its guidelines on the diagnosis and management of coeliac disease (CD) in adults.

The update, published in the United European Gastroenterology Journal, focuses particularly on diagnosis and reflects advances in laboratory techniques and diagnostic approaches to coeliac disease since 2019, when the previous ESsCD guidelines were released.

The most significant innovation in this update is the conditional introduction of a biopsy-free diagnostic pathway in patients with anti-TG2 IgA levels ≥10 × ULN, confirmed on a second blood sample.

In an accompanying editorial, Jason A. Tye-Din, a gastroenterologist at the University of Melbourne (Australia), highlights that the shift towards immune-based diagnostic testing reflects a broader conceptual shift in recognising coeliac disease as more than solely an intestinal disorder.

As Tye-Din notes, “intestinal villous atrophy is neither universally present nor pathognomonic for coeliac disease.” He further states that this major evolution away from an intestine-centred diagnostic focus may pave the way for additional immunological diagnostic approaches. Emerging biomarkers, such as interleukin-2 (IL-2), released following gluten exposure either in vivo or in vitro, show promise for enabling accurate diagnosis without the need for gluten challenge or intestinal biopsy-even in patients adhering to a gluten-free diet.

In the updated diagnostic framework, increasing importance is given to gluten-specific T cells. As Tye-Din explains, growing immunological and genomic evidence indicates that coeliac disease is a systemic, T cell-mediated condition.

This supports the use of T cell-based diagnostic tests and suggests that a redefinition of coeliac disease may be warranted-based on the presence of intestinal gluten-specific T-cell responses rather than enteropathy alone. Such a definition would align with the modern understanding of coeliac disease as a systemic condition, often associated with minimal enteropathy, and could help identify patients without overt histological changes who nevertheless benefit from a gluten-free diet.

The guidelines emphasise that decisions to omit endoscopy and duodenal biopsy, as well as the final diagnostic confirmation, should be made in a specialist setting. Shared decision-making with the patient is strongly recommended.

As diagnosis becomes increasingly reliant on serology, the importance of using validated and certified laboratory tests is underscored.

Regarding undiagnosed cases-which still outnumber diagnosed cases-the ESsCD guidelines support targeted screening of high-risk groups. Current evidence is considered insufficient to support population-wide screening.