INF-α Innate Immune Response to Gliadin

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Celiac Disease

Intervention / Treatment
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* Other: Intestinal biopsies


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Controls<br>Intestinal biopsies from controls, affected by gastroesophageal reflux, | Other: Intestinal biopsies<br>* 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.<br>|
| GCD CD (Gluten Containing Diet CD)<br>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<br>* 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.<br>|
| GFD CD (Gluten Free Diet CD)<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Celiac Disease; P31-43; Loxorubine; TLR7.