BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase prote...BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.展开更多
BACKGROUND Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease(CeD).Gluten immunogenic peptides(GIP)are resistant to gastrointe...BACKGROUND Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease(CeD).Gluten immunogenic peptides(GIP)are resistant to gastrointestinal digestion and are then excreted via the stool and urine.Most common detection methods applied in the follow-up visits for CeD patients such as serology tests,dietetic interviews,questionnaires,and duodenal biopsy have been proved to be inefficient,invasive,or inaccurate for evaluating gluten-free diet(GFD)compliance.Determination of excreted GIP in stool and urine has been developed as a non-invasive,direct,and specific test for GFD monitoring.AIM To summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD monitoring.METHODS PubMed and Web of Science searches were performed using the keywords“gluten immunogenic peptides”or“gluten immunogenic peptide”and a combination of the previous terms with“feces”,“stools”,“urine”,“celiac disease”,“gluten-free diet”,and“adherence”to identify relevant clinical studies published in English and Spanish between 2012 to January 2021.Reference lists from the articles were reviewed to identify additional pertinent articles.Published articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with CeD in comparison with other tools in use were included.Case reports,commentaries,reviews,conference papers,letters,and publications that did not focus on the aims of this review were excluded.RESULTS Total of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other tools.Studies included both children and adults diagnosed with CeD and healthy volunteers.Overall,these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could facilitate the follow-up of patients with CeD.Tools identified in this work included the CeD-specific serology,dietetic questionnaires,symptomatology,and the duodenal biopsy.Review of the literature revealed that the rates of GFD adherence may vary between 30%-93%using either stool or urine GIP determination,49%-96%by the serology,59%-94%using the dietetic questionnaires,56%-95%by the reported symptoms and 44%-76%with the duodenal biopsy.In addition,the association between the different methods and histological abnormalities(Marsh II-III)was found to be 33%-100%for GIP determination(stool and urine),25%-39%for CeD-specific serology,3%-50%for dietetic questionnaires,and 22%-28%for the symptomatology.CONCLUSION Excreted GIP detection is the precise approach for determining voluntary or involuntary gluten consumption in CeD patients preventing future complications arising from gluten exposure.展开更多
基金Supported by the Asociación de Celíacos y Sensibles al Gluten de Madrid,No.ACM2020)and Research Committee Argentine Society of Gastroenterology,No.2020.
文摘BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.
基金Supported by Ministerio de Ciencia e Innovación,No.DI-16-08943 and No.DI-17-09627.
文摘BACKGROUND Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease(CeD).Gluten immunogenic peptides(GIP)are resistant to gastrointestinal digestion and are then excreted via the stool and urine.Most common detection methods applied in the follow-up visits for CeD patients such as serology tests,dietetic interviews,questionnaires,and duodenal biopsy have been proved to be inefficient,invasive,or inaccurate for evaluating gluten-free diet(GFD)compliance.Determination of excreted GIP in stool and urine has been developed as a non-invasive,direct,and specific test for GFD monitoring.AIM To summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD monitoring.METHODS PubMed and Web of Science searches were performed using the keywords“gluten immunogenic peptides”or“gluten immunogenic peptide”and a combination of the previous terms with“feces”,“stools”,“urine”,“celiac disease”,“gluten-free diet”,and“adherence”to identify relevant clinical studies published in English and Spanish between 2012 to January 2021.Reference lists from the articles were reviewed to identify additional pertinent articles.Published articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with CeD in comparison with other tools in use were included.Case reports,commentaries,reviews,conference papers,letters,and publications that did not focus on the aims of this review were excluded.RESULTS Total of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other tools.Studies included both children and adults diagnosed with CeD and healthy volunteers.Overall,these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could facilitate the follow-up of patients with CeD.Tools identified in this work included the CeD-specific serology,dietetic questionnaires,symptomatology,and the duodenal biopsy.Review of the literature revealed that the rates of GFD adherence may vary between 30%-93%using either stool or urine GIP determination,49%-96%by the serology,59%-94%using the dietetic questionnaires,56%-95%by the reported symptoms and 44%-76%with the duodenal biopsy.In addition,the association between the different methods and histological abnormalities(Marsh II-III)was found to be 33%-100%for GIP determination(stool and urine),25%-39%for CeD-specific serology,3%-50%for dietetic questionnaires,and 22%-28%for the symptomatology.CONCLUSION Excreted GIP detection is the precise approach for determining voluntary or involuntary gluten consumption in CeD patients preventing future complications arising from gluten exposure.
