A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides

Celiac disease (CD) is a complex genetic disorder of the small intestine. The DQ2/DQ8 human leucocyte antigen (HLA) genes explain ∼40% of the genetic component of the disease, but the remaining non-HLA genes have not yet been identified. The key environmental factor known to be involved in the disease is gluten, a major protein present in wheat, barley, and rye. Integrating microarray data and linkage data from chromosome 6q21–22 revealed the prolyl endopeptidase ( PREP) gene as a potential CD candidate in the Dutch population. Interestingly, this gene encodes for the only enzyme that is able to cleave the proline-rich gluten peptides. To investigate the role of the human PREP gene as a primary genetic factor in CD, we conducted gene expression, sequence analysis, and genetic association studies of the PREP gene and determined PREP enzyme activity in biopsies from CD patients and controls. Sequence analysis of the coding region of the PREP gene revealed two novel polymorphisms. Genetic association studies using two novel polymorphisms and three known PREP variants excluded a genetic association between PREP and CD. Determination of PREP activity revealed weak but significant differences between treated and untreated CD biopsies ( P < 0.05). Our results from the association study indicate that PREP is not a causative gene for CD in the Dutch population. These are further supported by the activity determinations in which we observed no differences in PREP activity between CD patients and controls.

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Determination of gluten immunogenic peptides for the management of the treatment adherence of celiac disease: A systematic review

World Journal of Gastroenterology ◽

10.3748/wjg.v27.i37.6306 ◽

2021 ◽

Vol 27 (37) ◽

pp. 6306-6321

Author(s):

Laura Coto ◽

Irati Mendia ◽

Carolina Sousa ◽

Julio César Bai ◽

Angel Cebolla

Keyword(s):

Systematic Review ◽

Celiac Disease ◽

Treatment Adherence ◽

Immunogenic Peptides

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Detection of gluten immunogenic peptides and the Celiac Disease Adherence Test to monitor gluten-free diet: a pilot study

European Journal of Clinical Nutrition ◽

10.1038/s41430-021-01054-6 ◽

2022 ◽

Author(s):

Gry Irene Skodje ◽

Frida van Megen ◽

Marianne Stendahl ◽

Christine Henriksen ◽

Knut Erik Aslaksen Lundin ◽

...

Keyword(s):

Celiac Disease ◽

Pilot Study ◽

Gluten Free Diet ◽

Gluten Free ◽

Immunogenic Peptides ◽

Adherence Test

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Presence of DQ2.2 Associated with DQ2.5 Increases the Risk for Celiac Disease

Autoimmune Diseases ◽

10.1155/2016/5409653 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Lucas Malta Almeida ◽

Lenora Gandolfi ◽

Riccardo Pratesi ◽

Rosa Harumi Uenishi ◽

Fernanda Coutinho de Almeida ◽

...

Keyword(s):

At Risk ◽

T Cells ◽

Celiac Disease ◽

Disease Risk ◽

Disease Development ◽

Immunogenic Peptides ◽

Immune Mediated ◽

Hla Dq ◽

Genetically Determined

Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when p<0.05. Disease risk was expressed as 1 : N for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.2 (β2/β2 or β2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.2 (β2/β2) showed high CD risk of 1 : 10 (p<0.0001). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5.

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Efficient Hydrolysis of Gluten-Derived Celiac Disease-Triggering Immunogenic Peptides by a Bacterial Serine Protease from Burkholderia gladioli

Biomolecules ◽

10.3390/biom11030451 ◽

2021 ◽

Vol 11 (3) ◽

pp. 451

Author(s):

Yu-You Liu ◽

Cheng-Cheng Lee ◽

Jun-Hao Hsu ◽

Wei-Ming Leu ◽

Menghsiao Meng

Keyword(s):

Celiac Disease ◽

Autoimmune Disorder ◽

Health Condition ◽

Kinetic Assay ◽

Peptide Bonds ◽

E Coli ◽

Burkholderia Gladioli ◽

Immunogenic Peptides ◽

Oral Enzyme Therapy ◽

Toxic Peptides

Celiac disease is an autoimmune disorder triggered by toxic peptides derived from incompletely digested glutens in the stomach. Peptidases that can digest the toxic peptides may formulate an oral enzyme therapy to improve the patients’ health condition. Bga1903 is a serine endopeptidase secreted by Burkholderia gladioli. The preproprotein of Bga1903 consists of an N-terminal signal peptide, a propeptide region, and an enzymatic domain that belongs to the S8 subfamily. Bga1903 could be secreted into the culture medium when it was expressed in E. coli. The purified Bga1903 is capable of hydrolyzing the gluten-derived toxic peptides, such as the 33- and 26-mer peptides, with the preference for the peptide bonds at the carbonyl site of glutamine (P1 position). The kinetic assay of Bga1903 toward the chromogenic substrate Z-HPQ-pNA at 37 °C, pH 7.0, suggests that the values of Km and kcat are 0.44 ± 0.1 mM and 17.8 ± 0.4 s−1, respectively. The addition of Bga1903 in the wort during the fermentation step of beer could help in making gluten-free beer. In summary, Bga1903 is usable to reduce the gluten content in processed foods and represents a good candidate for protein engineering/modification aimed to efficiently digest the gluten at the gastric condition.

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