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

Anderson, Robert P

doi:10.1080/1744666x.2021.2006636

Cited by 7 publications

(9 citation statements)

References 158 publications

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“…There is a strong case to re‐evaluate mucosal histology as the arbiter of disease activity and identify therapeutic targets associated with the reduction of long‐term complications. Coeliac disease is fundamentally an immune illness, the hallmark of which is aberrant immunity to gluten, 79,168 and small intestinal mucosal damage is an important but not universal feature of active disease associated with gluten‐specific immunity (an example is dermatitis herpetiformis, where enteropathy is not always present). Small intestinal histology is an imperfect “gold standard” diagnostic test, and the value of an immune (serological), non‐biopsy approach to diagnosis is now embedded in some paediatric guidelines 137 .…”

Section: Future Directionsmentioning

confidence: 99%

Review article: Follow‐up of coeliac disease

Tye–Din

2022

Aliment Pharmacol Ther

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Coeliac disease is a lifelong immune-mediated enteropathy associated with important systemic manifestations. 1,2 A strict gluten-free diet (GFD) is the cornerstone of management but does not resolve the underlying immune cause of coeliac disease. 3 The GFD imparts a substantial treatment burden, 4 and many patients fail to achieve complete symptom or mucosal remission. As coeliac disease is associated with increased morbidity and modestly increased mortality, periodic medical follow-up is considered a crucial component of patient care [5][6][7][8] but this is compromised by the paucity of evidence to inform best-practice approaches. 9,10 As a result, real-world follow-up is often inconsistent or absent altogether. [11][12][13] For many chronic illnesses, such as type 1 diabetes, the importance of maintaining long-term follow-up to assess disease status, treatment efficacy and monitor for complications is well established in the medical community, however, for coeliac disease, this is typically not the case, even though the monitoring goals are the same. 5,6,7,8,14 For patients, the key goals of treatment are to resolve symptoms, reduce the risk of complications and achieve optimal quality of life, and for clinicians, disease remission also encompasses healing of the enteropathy. Effective models of care that leverage local medical and allied health expertise, ideally involving a gastroenterologist, dietitian and primary care provider, will support these goals but willThe Handling Editor for this article was Professor Peter Gibson, and it was accepted for publication after full peer-review.

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Section: Future Directionsmentioning

confidence: 99%

Review article: Follow‐up of coeliac disease

Tye–Din

2022

Aliment Pharmacol Ther

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“…Mechanistic studies initially focused on A‐gliadin, a member of the α‐gliadin family that was the first gluten protein to be fully sequenced 82 . As more gluten genes were cloned and support for the adaptive immune paradigm of CD strengthened, 2,83 interest has shifted from incriminating a single immunodominant T cell‐stimulatory peptide (e.g. 33mer α‐gliadin peptide) 84 to understanding the relationship between peptide targets for a conserved but diverse CD4+ T cell and B cell response to gluten associated with autoreactive B cells specific for TG2 85–87 …”

Section: Pathogenesismentioning

confidence: 99%

“…Implicit in many potential future developments in diagnosis is a consensus being reached on the immunological basis for CD. 2 This could allow acceptance of a suite of blood tests measuring gluten-specific adaptive immunity complementary to serology and accelerate the move to "biopsy-free" diagnosis as well as overcoming the need for regular gluten consumption to diagnose CD. 8-10…”

Section: Introduction 1| Backgroundmentioning

confidence: 99%

“…An unresolved challenge in clinical practice is to understand who to test given that many individuals with CD remain unrecognised, and how to assess those who avoid dietary gluten and would be better suited to other diets or interventions. Implicit in many potential future developments in diagnosis is a consensus being reached on the immunological basis for CD 2 . This could allow acceptance of a suite of blood tests measuring gluten‐specific adaptive immunity complementary to serology and accelerate the move to “biopsy‐free” diagnosis as well as overcoming the need for regular gluten consumption to diagnose CD 8–10 …”

Section: Introductionmentioning

confidence: 99%

“…Coeliac disease (CD) is an immune‐mediated gluten‐dependent enteropathy affecting the proximal small intestine, 1 which is closely linked to a cell‐mediated hypersensitivity reaction to deamidated gluten 2 . Depending on duodenal histology, serology findings and severity of symptoms, CD is defined as potential, asymptomatic, symptomatic, classic, non‐classic or refractory (Table 1).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Review article: Diagnosis of coeliac disease: a perspective on current and future approaches

Anderson

2022

Aliment Pharmacol Ther

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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.

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Evolution in coeliac disease diagnosis and management

Tye‐Din

2024

JGH Open

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The traditional gut‐centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease ‐ well demonstrated in children ‐ are growing for adults. Novel biomarkers such as interleukin‐2 that identify the gluten‐specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge. Asymptomatic disease and manifestations outside the gut pose considerable challenges for diagnosis using a case‐finding strategy and enthusiasm for population screening is growing. The gluten‐free diet remains a highly restrictive treatment and there is a paucity of controlled data to inform a safe gluten intake threshold. Ongoing symptoms and enteropathy are common and require systematic evaluation. Slowly‐responsive disease is prevalent in the older patient diagnosed with coeliac disease, and super‐sensitivity to gluten is an emerging concept that may explain many cases of nonresponsive disease. While there is great interest in developing novel therapies for coeliac disease, no drug has yet been registered. Efficacy studies are generally assessing drugs in patients with treated coeliac disease who undergo gluten challenge or in patients with nonresponsive disease; however, substantial questions remain around specific endpoints relevant for patients, clinicians and regulatory agencies and optimal trial design. Novel immune tools are providing informative readouts for clinical trials and are now shaping their design.

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

Cited by 7 publications

References 158 publications

Review article: Follow‐up of coeliac disease

Review article: Follow‐up of coeliac disease

Review article: Diagnosis of coeliac disease: a perspective on current and future approaches

Evolution in coeliac disease diagnosis and management

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