Coeliac disease—a meeting point for genetics, immunology, and protein chemistry

  title={Coeliac disease—a meeting point for genetics, immunology, and protein chemistry},
  author={AllanMci. Mowat},
  journal={The Lancet},
  • A. Mowat
  • Published 12 April 2003
  • Medicine, Biology
  • The Lancet
Anti-tissue transglutaminase antibodies and their role in the investigation of coeliac disease
This review examines the evidence for adopting IgA anti-tissue TGA as the first-line diagnostic test for CD and recommends a laboratory algorithm for the use and interpretation of TGA to enable the clinical laboratory to play a full part in detecting and monitoring a disorder that is eminently treatable once the diagnosis has been considered and confirmed.
Genetic and functional analysis of pyroglutamyl-peptidase I in coeliac disease
The results uniformly indicate that PGPEP1 is not involved in the aetiology and pathology of CD, and an impaired enzyme function caused by genetic alterations might increase the amount of immunogenic gluten peptides.
Coeliac disease: a diverse clinical syndrome caused by intolerance of wheat, barley and rye
Current advice is that dietary adherence is necessary to avoid the long-term complications, which are, principally, osteoporosis and small bowel lymphoma, but risk of these complications diminishes very considerably in patients who are on a gluten-free diet.
Recent advances in coeliac disease genetics
Around 1 in 100 individuals of European descent have coeliac disease. An immune response in the small intestine is generated to fragments of “gluten”, storage proteins found in wheat, rye and barley.
Unraveling the molecular genetic aspects of intestinal inflammatory disorders
A new, simple and cost-effective method to screen for HLA variants, using SNPs that are in linkage disequilibrium with the risk variants, and found that the gene myosin IXB is involved in celiac disease, probably by enhancing the permeability of the intestinal barrier.
Celiac disease diagnosis and gluten-free food analytical control
Since the current treatment consists of a life-long gluten-free diet, which leads to significant clinical and histological improvement, the standardization of an assay to assess in an unequivocal way gluten in gluten- free foodstuff is of major importance.
Celiac Disease and Immunogenic Wheat Gluten Peptides and the Association of Gliadin Peptides with HLA DQ2 and HLA DQ8
ABSTRACT Wheat consists mainly of gluten with about 30% gliadin and 50% glutenin, which give gluten its unique viscoelastic properties and also mainly associated with the cause of celiac disease.
Celiac Disease Pathogenesis: The Proinflammatory Cytokine Network
The involvement of activation pathways in the context of the pathogenesis of celiac disease are described, which can drive the inflammatory response probably sustained by IL-18, IL-21, and perhaps IL-27 through STAT1 and STAT5 pathways.
Potential of transglutaminase 2 as a therapeutic target
Beneficial effects of enzyme activity inhibition have been observed in neurodegeneration and fibrosis in vivo models by delivery of the competitive inhibitor cystamine and more recently designed inhibitors, which irreversibly bind the active site cysteine residue.


The Intestinal T Cell Response to α-Gliadin in Adult Celiac Disease Is Focused on a Single Deamidated Glutamine Targeted by Tissue Transglutaminase
Modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide–MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.
Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease
Evidence is provided for a new role of Transglutaminase in the common, HLA-DQ2 (and DQ8) associated celiac disease and it is demonstrated that TGase mediates its effect through an ordered and specific deamidation of gliadins.
Structural Basis for Gluten Intolerance in Celiac Sprue
A 33-mer peptide was identified that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue patients, and could be detoxified in in vitro and in vivo assays by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for CeliacSprue.
Glutenin is involved in the gluten‐driven mucosal T cell response
Using high‐performance liquid chromatography purification steps of gluten with a T cell bioassay and mass spectral analyses, a glutenin peptide is identified that activates T cells from the small intestine of a coeliac disease patient and results in the secretion of large amounts of IFN‐γ.
The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides.
The diversity of the GLU-specific T-cell response is far greater than was previously appreciated, and the observation that T- cell responses to 3 of the novel peptides are independent of deamidation indicates thatT-cell responses can be initiated toward native GLU peptides.
Basic mechanisms and clinical implications of oral tolerance.
  • A. Mowat
  • Biology, Medicine
    Current opinion in gastroenterology
  • 1999
Recent evidence that fed antigens are presented to CD4(+) T cells by antigen-presenting cells (APCs) that lack costimulatory activity, resulting in partial activation of T cells followed by a state of unresponsiveness is discussed.
Oral tolerance.
Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis, arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy and no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate in MS.
Expanding dendritic cells in vivo enhances the induction of oral tolerance.
Surprisingly, mice treated with Flt3L to expand DC exhibited more profound systemic tolerance after they were fed soluble Ag, suggesting a pivotal role for DC during the induction of tolerance following mucosal administration of Ag.
Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer
Typing of DNA from 94 unrelated children with celiac disease (CD) with HLA-DQA1 and -DQB1 allele-specific oligonucleotide probes revealed that all but one (i.e., 98.9%) may share a particular