INF-α Innate Immune Response to Gliadin

A Gliadin Peptide Regulated the INF-α Immune Response in Celiac Small Intestine and in an En-terocyte Cell Line

Background & Aims The enteropathy in Celiac Disease (CD) is due the adaptive and to the innate immune response to gliadin peptides. Gliadin peptide P31-43 activates innate immune response and interferes with vesicular trafficking. Type 1 interferons (INFs) and viral infections play a role in CD pathogenesis. In this paper investigators investigated the role of P31-43 in the activation of the INF-α pathway.

Methods Small intestinal biopsies of CD patients both with active disease on gluten containing diet (GCD) and in remission phase of the disease on a gluten free diet (GFD) and controls were analyzed before and after culture with P31-43. The levels of toll like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), myxovirus resistance protein 1 (MxA) and nuclear factor-κB (NF-κB) proteins and INF-α mRNA was analyzed in intestinal biopsies.

Study Overview

• Status: Completed
• Conditions: Celiac Disease
• Intervention / Treatment: Other: Intestinal biopsies

Detailed Description

Intestinal biopsies from CD patients and controls were obtained after EGDS performed during routine analysis. The biopsies were immediately immersed in culture medium (Dulbecco's modified medium, DMEM) in a falcon tube and kept for 16h at 37 C before cultivation. Biopsies were cultivated as described in Barone MV1, Caputo I, Ribecco MT, Maglio M, Marzari R, Sblattero D, Troncone R, Auricchio S, Esposito C. Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease. Gastroenterology. 2007,132(4):1245-53.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • Riccardo Troncone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

For organ culture studies, biopsy fragments from duodenum were obtained from CD patients with villous atrophy on GCD, controls, affected by gastroesophageal reflux, and CD patients on GFD. Age range for all subjects was 2-17 years.

Description

Inclusion Criteria:

biopsy fragments from duodenum were obtained from CD patients with villous atrophy on GCD, controls, affected by gastroesophageal reflux, and CD patients on GFD.

Exclusion Criteria:

other inflammatory intestinal diseases

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; Intestinal biopsies from controls, affected by gastroesophageal reflux,	Other: Intestinal biopsies; Intestinal biopsies obtained from Patients and Controls by EGDS. The patients and controls had the intestinal biopsies as a diagnostic step or routine check independently from the present study. For this study 3 additional biopsies samples were done in patients and controls that signed the informed consent.
GCD CD (Gluten Containing Diet CD); Intestinal biopsies from GFD patients had with negative serology (anti-tTg antibodies between 0 and 1.5 U/ml and EMA negative) and normal biopsy (Marsh T0-1).	Other: Intestinal biopsies; Intestinal biopsies obtained from Patients and Controls by EGDS. The patients and controls had the intestinal biopsies as a diagnostic step or routine check independently from the present study. For this study 3 additional biopsies samples were done in patients and controls that signed the informed consent.
GFD CD (Gluten Free Diet CD); Intestinal biopsies from GCD-CD patients with villous atrophy (Marsh T3a-c) had positive serology (anti-tTg antibodies >30 U/ml and EMA positive) ).	Other: Intestinal biopsies; Intestinal biopsies obtained from Patients and Controls by EGDS. The patients and controls had the intestinal biopsies as a diagnostic step or routine check independently from the present study. For this study 3 additional biopsies samples were done in patients and controls that signed the informed consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Mxa and INF alpha proteins in CD biopsies compared to controls	Intestinal biopsies from CD patients and controls were used to study protein levels of MxA and INF-alpha by western blot. MxA protein levels were compared to tubulin and ERK as loading control. Student t test was used to analyse the data.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Principal Investigator: M.Vittoria Barone, Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2013
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Celiac Disease; P31-43; Loxorubine; TLR7.
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: Innate immunity CD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The statistical data concerning the intestinal biopsies will be published on international journal
• IPD Sharing Time Frame: the statistical analysis will be published
• IPD Sharing Access Criteria: Publication on international journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No