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June 29, 2022

Adaptive Immune Paradigm

Emergence of an adaptive immune paradigm to explain celiac disease: a perspective on new evidence and implications for future interventions and diagnosis.


Abstract


Introduction


Recent patient studies have shown that gluten-free diet is less effective in treating celiac disease than previously believed, and additionally patients remain vulnerable to gluten-induced acute symptoms and systemic cytokine release. Safe and effective pharmacological adjuncts to gluten-free diet are in preclinical and clinical development. Clear understanding of the pathogenesis of celiac disease is critical for drug target identification, establishing efficacy endpoints and to develop noninvasive biomarkers suitable to monitor and potentially diagnose celiac disease.


Areas covered


The role and clinical effects of CD4+ T cells directed against deamidated gluten in the context of an ‘adaptive immune paradigm’ are reviewed. Alternative hypotheses of gluten toxicity are discussed and contrasted. In the context of recent patient studies, implications of the adaptive immune paradigm for future strategies to prevent, diagnose, and treat celiac disease are outlined.


Expert Opinion


Effective therapeutics for celiac disease are likely to be approved and necessitate a variety of new clinical instruments and tests to stratify patient need, monitor remission, and confirm diagnosis in uncertain cases. Sensitive assessments of CD4+ T cells specific for deamidated gluten are likely to play a central role in clinical management, and to facilitate research and pharmaceutical development.


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Diagnosis of Celiac Disease

By Katie George • July 24, 2022
Review article: Diagnosis of coeliac disease: a perspective on current and future approaches.  Summary Diagnostics will play a central role in addressing the ongoing dramatic rise in global prevalence of coeliac disease, and in deploying new non-dietary therapeutics. Clearer understanding of the immunopathogenesis of coeliac disease and the utility of serology has led to partial acceptance of non-biopsy diagnosis in selected cases. Non-biopsy diagnosis may expand further because research methods for measuring gluten-specific CD4+ T cells and the acute recall response to gluten ingestion in patients is now relatively straightforward. This perspective on diagnosis in the context of the immunopathogenesis of coeliac disease sets out to highlight current consensus, limitations of current practices, gluten food challenge for diagnosis and the potential for diagnostics that measure the underlying cause for coeliac disease, gluten-specific immunity.

Opportunities & Milestones

By Andor Rosenberg • June 29, 2022
Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease.  Abstract Progress has been made in understanding coeliac disease, a relatively frequent and underappreciated immune-mediated condition that occurs in genetically predisposed individuals. However, several gaps remain in knowledge related to diagnosis and management. The gluten-free diet, currently the only available management, is not curative or universally effective (some adherent patients have ongoing duodenal injury). Unprecedented numbers of emerging therapies, including some with novel tolerogenic mechanisms, are currently being investigated in clinical trials. In March 2020, the Celiac Disease Foundation and the Society for the Study of Celiac Disease convened a consensus workshop to identify high-yield areas of research that should be prioritized. Workshop participants included leading experts in clinical practice, academia, government and pharmaceutical development, as well as representatives from patient support groups in North America. This Roadmap summarizes key advances in the field of coeliac disease and provides information on important discussions from the consensus approach to address gaps and opportunities related to the pathogenesis, diagnosis and management of coeliac disease. The morbidity of coeliac disease is often underestimated, which has led to an unmet need to improve the management of these patients. Expanded research funding is needed as coeliac disease is a potentially curable disease. Click to read the full article ...
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