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IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin.

ABSTRACT: BACKGROUND: In coeliac disease (CD) patients, the dominant DQ2-Alpha-I-gliadin peptide recognised by CD4 T cells is contained within peptide sequence 57-73 (p57-73) of Alpha-gliadin. This peptide sequence is also located within a 33-mer protease resistant gliadin fragment and therefore is likely to play an important role in the pathogenesis of CD. AIMS: Our aim was to determine whether a B cell epitope was present within the immunodominant T cell epitope of Alpha-gliadin and, if so, to elucidate its sequence and determine the importance of deamidation and/or modification of the amino acid at position 65 for IgA binding. PATIENTS AND METHODS: A cohort of CD patients, disease controls, and healthy individuals were examined. Serum IgA antibodies to the native and modified p57-73 fragment of Alpha-gliadin were analysed using enzyme linked immunosorbent assays. Peptide scanning experiments were further used to elucidate the B cell epitope. RESULTS AND CONCLUSION: IgA antibodies to p57-73 were found in 29/72 (40.2%) endomysial antibody positive patients, all of whom had CD. The peptide antibody appeared to be present when patients were on a diet containing gluten and declined on a gluten free diet. The p57-73 antibody was very specific for CD (98%) and had a sensitivity of 56%. The amino acid at position 65 was not important for IgA binding but was crucial for T cell recognition of p57-73. Pentapeptide PXPQP emerges as a potentially strong candidate for the IgA binding motif in this region of Alpha-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope.

SUBMITTER: Bateman EA

PROVIDER: S-EPMC1774203 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature

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IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin.

Bateman E A L EA Ferry B L BL Hall A A Misbah S A SA Anderson R R Kelleher P P

Gut 20040901 9

<h4>Background</h4>In coeliac disease (CD) patients, the dominant DQ2-Alpha-I-gliadin peptide recognised by CD4 T cells is contained within peptide sequence 57-73 (p57-73) of Alpha-gliadin. This peptide sequence is also located within a 33-mer protease resistant gliadin fragment and therefore is likely to play an important role in the pathogenesis of CD.<h4>Aims</h4>Our aim was to determine whether a B cell epitope was present within the immunodominant T cell epitope of Alpha-gliadin and, if so, ...[more]

PMID: 15306584

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Project description:BackgroundInternational guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach.MethodsGroup 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed.ResultsIn group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease.ConclusionSimtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies.Trial registrationThe group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13(th) July 2016;Trial registration numberNCT02834429 .

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IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin.

Publications

IgA antibodies of coeliac disease patients recognise a dominant T cell epitope of A-gliadin.

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