NCT05469971

KIR Genes and Non-Celiac Wheat Sensitivity

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

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 170 (actual)
• Sponsor: University of Palermo · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: —

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.

Detailed description

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. Despite the great interest in NCGS, much remains unknown about its pathogenesis. Some studies seem to suggest that wheat components other than gluten (i.e. amylase/trypsin inhibitors, ATIs) can be responsible of symptom's triggering, and therefore the term "non-celiac wheat sensitivity" (NCWS) has been proposed as a more appropriate label. NCWS pathogenesis has been attributed to very different mechanisms: innate or adaptive immunity, incomplete digestion and/or absorption of fermentable oligosaccharides and disaccharides, monosaccharides, and polyols, and, finally, psychological effect. Although NCWS might be considered in its clinical features like CD, to date, no data are available about genes that confer a higher genetic predisposition to the disease. It is known that, in contrast to CD, patients with NCWS do not have a characteristic Human Leucocyte Antigens (HLA) genotype/phenotype, even if HLA DQ2/DQ8 alleles are present in 40-50% of these patients, a value higher than that of the general population (30%). Many studies ascertained the importance of innate immunity and of Natural Killer (NK) cells in the pathogenesis of NCWS. KIRs (Killer Immunoglobulin-like Receptors) regulate the activation of NK cells through their interaction with 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. More in general, several studies have shown that haplotypes containing predominantly activator genes confer protection against viral infections and susceptibility to the development of autoimmune and neoplastic diseases. In the context of CD, NK cells are one of the main components of innate immunity and are involved in the destruction of epithelial cells and their cytotoxic activity is closely related to the function of KIRs. 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.

Conditions

• Non-celiac Wheat Sensitivity

Interventions

Type	Name	Description
GENETIC	KIR genotyping	DNA extraction and KIR genotyping by KIR SSO Genotyping Test (One Lambda, Thermo Fisher, Monza, Italy).

Timeline

• Start date: 2022-11-01
• Primary completion: 2023-06-30
• Completion: 2023-09-30
• First posted: 2022-07-22
• Last updated: 2023-11-28

Locations

4 sites across 1 country: Italy