Interplay between the toxic alpha-gliadin peptide 31-43 and type 2 transglutaminase enzyme in Celiac Disease

2019 ◽  
Vol 29 (8) ◽  
pp. 873
Author(s):  
Gaetana Paolella ◽  
Marilena Lepretti ◽  
Stefania Martucciello ◽  
Lillà Lionetti ◽  
Carla Esposito ◽  
...  
2020 ◽  
Vol 21 (10) ◽  
pp. 3673 ◽  
Author(s):  
Stefania Martucciello ◽  
Silvia Sposito ◽  
Carla Esposito ◽  
Gaetana Paolella ◽  
Ivana Caputo

Celiac disease (CD) is a common intestinal inflammatory disease involving both a genetic background and environmental triggers. The ingestion of gluten, a proteic component of several cereals, represents the main hexogen factor implied in CD onset that involves concomitant innate and adaptive immune responses to gluten. Immunogenicity of some gluten sequences are strongly enhanced as the consequence of the deamidation of specific glutamine residues by type 2 transglutaminase (TG2), a ubiquitous enzyme whose expression is up-regulated in the intestine of CD patients. A short gluten sequence resistant to intestinal proteases, the α-gliadin peptide 31-43, seems to modulate TG2 function in the gut; on the other hand, the enzyme can affect the biological activity of this peptide. In addition, an intense auto-immune response towards TG2 is a hallmark of CD. Auto-antibodies exert a range of biological effects on several cells, effects that in part overlap with those induced by peptide 31-43. In this review, we delineate a scenario in which TG2, anti-TG2 antibodies and peptide 31-43 closely relate to each other, thus synergistically participating in CD starting and progression.


2018 ◽  
Vol 75 (22) ◽  
pp. 4107-4124 ◽  
Author(s):  
Stefania Martucciello ◽  
Gaetana Paolella ◽  
Carla Esposito ◽  
Marilena Lepretti ◽  
Ivana Caputo
Keyword(s):  

2012 ◽  
Vol 55 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Lourdes Mozo ◽  
Jesús Gómez ◽  
Esther Escanlar ◽  
Carlos Bousoño ◽  
Carmen Gutiérrez

Endoscopy ◽  
2019 ◽  
Vol 52 (06) ◽  
pp. E195-E197
Author(s):  
Jean-Philippe Le Mouel ◽  
Mathurin Fumery ◽  
Sami Hakim ◽  
Clara Yzet ◽  
Alexandra Dervaux ◽  
...  

2018 ◽  
Vol 113 (8) ◽  
pp. 1238-1246 ◽  
Author(s):  
Michelle S. Lau ◽  
Peter D. Mooney ◽  
William L. White ◽  
Michael A. Rees ◽  
Simon H. Wong ◽  
...  

2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e14-e14
Author(s):  
Michelle Gould ◽  
Herbert Brill ◽  
Margaret Marcon ◽  
Catharine Walsh

Abstract BACKGROUND Celiac disease (CD) is an autoimmune enteropathy triggered by gliadin. The gold standard for diagnosis is small bowel biopsy. Screening with serologic markers to identify endoscopic candidates is commonly completed by paediatricians. The most common serologic marker used for screening is IgA anti-Tissue Transglutaminase (TTG) antibodies. Antibodies to deamidated gliadin peptide (DGP) is a newer assay with studies demonstrating a diagnostic performance similar to anti-TTG. In Canada, this assay has been added to many laboratory’s celiac screening panels. There is little evidence however regarding the usefulness of an isolated positive anti-DGP result in paediatric patients and no study has systematically assessed the presence of biopsy proven CD in solely anti-DGP positive paediatric patients. OBJECTIVES We sought to determine the positive predictive value of anti-DGP for biopsy proven CD in paediatric patients with negative TTG IgA testing. DESIGN/METHODS A multi-center retrospective review of children referred to three centers in Ontario, Canada between January 2015 and December 2016 who had isolated anti-IgG DGP positive CD serology was completed. To be included, patients required serology positive for DGP IgG and negative for all other celiac serologic tests, as well as a duodenal biopsy while on a gluten-containing diet. The positive predictive value of isolated anti-DGP was calculated. RESULTS A total of 83 patients were identified with anti-DGP positive, anti-TTG negative serology. Of these, 40 patients underwent endoscopy. Only 1 patient had findings consistent with CD on biopsy (Marsh 3B histology), yielding a positive predictive value of 2.5%. This patient was IgA deficient. Amongst the cohort of IgA sufficient patients (N=25), the positive predictive value of anti-DGP serology was 0%. One additional patient who was IgA sufficient had findings in keeping with Marsh 2 histology, but repeat TTG and DGP testing was negative. Five patients were found to be IgA deficient at the time of serologic testing, 25 were IgA sufficient and 10 did not have a measured IgA. CONCLUSION Isolated positive DGP IgG serology has a poor positive predictive value for CD, especially in IgA sufficient individuals. For this reason, DGP IgG testing should not be completed as part of the initial screening for celiac disease in the paediatric population unless a compelling reason, such as IgA deficiency or age under 2 years, is present, in order to prevent unnecessary invasive follow-up testing and costs to patients and the health care system.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
B. Admou ◽  
L. Essaadouni ◽  
K. Krati ◽  
K. Zaher ◽  
M. Sbihi ◽  
...  

The nonclassic clinical presentation of celiac disease (CD) becomes increasingly common in physician’s daily practice, which requires an awareness of its many clinical faces with atypical, silent, and latent forms. Besides the common genetic background (HLA DQ2/DQ8) of the disease, other non-HLA genes are now notably reported with a probable association to atypical forms. The availability of high-sensitive and specific serologic tests such as antitissue transglutuminase, antiendomysium, and more recent antideamidated, gliadin peptide antibodies permits to efficiently uncover a large portion of the submerged CD iceberg, including individuals having conditions associated with a high risk of developing CD (type 1 diabetes, autoimmune diseases, Down syndrome, family history of CD, etc.), biologic abnormalities (iron deficiency anemia, abnormal transaminase levels, etc.), and extraintestinal symptoms (short stature, neuropsychiatric disorders, alopecia, dental enamel hypoplasia, recurrent aphtous stomatitis, etc.). Despite the therapeutic alternatives currently in developing, the strict adherence to a GFD remains the only effective and safe therapy for CD.


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