Contribution of KIR Genes on the Genetic Predisposition to Non-Celiac Wheat Sensitivity

Status: Completed
Location: See all (4) locations...
Intervention Type: Genetic
Study Type: Observational
SUMMARY

Non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extraintestinal symptoms which are triggered by gluten ingestion in the absence of celiac disease (CD) and wheat allergy. In the last years studies suggested that wheat components other than gluten can be responsible of symptom's triggering, thus the term non-celiac wheat sensitivity (NCWS) has been proposed as a more appropriate label. To date, different pathogenetic mechanisms have been proposed, but no conclusive data have been reported; among these, some study groups a possible role of innate immunity and of Natural Killer (NK) cells. KIR (Killer Immunoglobulin-like Receptors) regulate the activation of NK cells through their interaction with Human Leucocyte Antigens (HLA). Both KIR and HLA loci are highly polymorphic, and, in the case of KIR, two main haplotypes have been identified: A and B. Haplotype A is the simplest and correlates mainly with NK inhibition, while haplotype B has a variable number of genes, most of which activate NK cells. The investigators hypothesis is that the genetic variants of KIR, which define the haplotype inhibitor or activator, can affect the development and the course of NCWS too. Thus, the researchers aimed to:1. Identify putative KIR genetic variants in NCWS patients (50 subjects) respect to celiac disease patients (50 subjects) and blood donors (50 subjects); 2. Evaluate the possible association of KIR genetic variants with specific clinical manifestations of patients with NCWS.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 65
View:

⁃ age \>18 and \<65 years

• subjects with gluten/wheat-dependent symptoms, both intestinal and extra-intestinal

• negativity of anti-deamidated gliadin protein (DGP) immunoglobulins (Ig) class A (IgA) and IgG, anti-tissue transglutaminase (tTG) IgA and IgG, Endomysium antibody (EMA)

• absence of villous atrophy at the duodenal level, documented in all patients with HLA DQ2 and/or DQ8 (therefore, regardless of the negativity of CD-specific serum antibodies), evaluated when patients had a minimum intake of 100 grams of pasta and/or bread a day, for at least 45 days

• absence of wheat allergy (negative prick-test and/or specific serum IgE assay for wheat, gluten and gliadin)

• resolution of symptoms with a strict standard elimination diet, i.e., oligoantigenic (without wheat, cow's milk, egg, tomato and chocolate, and other foods self-reported by the patient as causing symptoms), for at least 4 weeks, followed by the reappearance of the same after a Double-Blind Placebo-Controlled Challenge (DBPCC) with gluten/wheat

• complete medical records

• duration of follow-up greater than 12 months after initial diagnosis and at least 2 outpatient visits during the follow-up period.

Locations
Other Locations
Italy
Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo
Palermo
Department of Internal Medicine, University Hospital of Palermo
Palermo
Internal Medicine Division of the Cervello-Villa Sofia Hospital
Palermo
Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
Sciacca
Time Frame
Start Date: 2022-11-01
Completion Date: 2023-09-30
Participants
Target number of participants: 170
Treatments
NCWS patients
The researchers will enrol NCWS, presenting with IBS and/or dyspepsia-like symptoms, according to the Rome IV criteria (20). These patients were diagnosed by DBPC wheat challenge between January 2010 and June 2022 in three tertiary centers for gluten-related disorders (Department of Internal Medicine, University Hospital of Palermo, Italy; Department of Internal Medicine, Cervello Hospital of Palermo, Italy, and Department of Internal Medicine, Hospital of Sciacca, Agrigento, Italy.
Celiac disease
The researchers will enrol CD patients diagnosed between January 2010 and June 2022 in three tertiary centers for gluten-related disorders (Department of Internal Medicine, University Hospital of Palermo, Italy; Department of Internal Medicine, Cervello Hospital of Palermo, Italy, and Department of Internal Medicine, Hospital of Sciacca, Agrigento, Italy.
Blood donors
The researchers will enroll blood donors from the Transfusion Centre of the University Hospital of Palermo, Italy.
Sponsors
Leads: University of Palermo

This content was sourced from clinicaltrials.gov