NCT05469971|Completed
KIR Genes and Non-Celiac Wheat Sensitivity
Contribution of KIR Genes on the Genetic Predisposition to Non-Celiac Wheat Sensitivity
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Contribution of KIR Genes on the Genetic Predisposition to Non-Celiac Wheat Sensitivity
Sponsor study identifier
observational
170
1 country
4
Study Start
November 1, 2022
Actual (reported)Primary Completion
June 30, 2023
Actual (reported)Study Completion
September 30, 2023
Actual (reported)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.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
September 30, 2023
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
July 11, 2022
Actual (reported)July 22, 2022
Actual (reported)November 1, 2022
Actual (reported)June 30, 2023
Actual (reported)September 30, 2023
Actual (reported)KIR genetic variants in NCWS patients respect to CD patients and blood donors
Evaluation of the presence and prevalence of KIR genetic variants (haplotype A or B) in NCWS patients respect to CD patients and blood donors.
Through study completion, an average of 1 year
Association between KIR genetic variants and clinical manifestation of NCWS patients
Association between KIR genetic variants and the clinical symptoms (irritable bowel syndrome-like, functional dyspepsia-like, and extraintestinal) of NCWS patients.
Through study completion, an average of 1 year
Association between KIR genetic variants and associated autoimmune diseases of NCWS patients
Association between KIR genetic variants and the associated autoimmune diseases (e.g., autoimmune thyroiditis) of NCWS patients.
Through study completion, an average of 1 year
Association between KIR genetic variants and coexistent other food allergies/intolerances of NCWS patients
Association between KIR genetic variants and the coexistent other food allergies/intolerances (e.g., self-reported milk intolerance) of NCWS patients.
Through study completion, an average of 1 year
Association between KIR genetic variants and HLA DQ2-DQ8 genotypes of NCWS patients.
Association between KIR genetic variants and the HLA DQ2-DQ8 genotypes of NCWS patients.
Through study completion, an average of 1 year
Association between KIR genetic variants and duodenal histology of NCWS patients.
Association between KIR genetic variants and the duodenal histology (i.e., Marsh-Oberuber classification) of NCWS patients.
Through study completion, an average of 1 year
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.
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.
The researchers will enroll blood donors from the Transfusion Centre of the University Hospital of Palermo, Italy.
DNA extraction and KIR genotyping by KIR SSO Genotyping Test (One Lambda, Thermo Fisher, Monza, Italy).
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
50 NCWS patients, 50 CD patients, and 50 healthy blood donors.
Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca
Sciacca, Agrigento, 92019, Italy
Internal Medicine Division of the "Cervello-Villa Sofia" Hospital
Palermo, PA, 90146, Italy
Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo
Palermo, 90127, Italy
Department of Internal Medicine, University Hospital of Palermo
Palermo, 90129, Italy
Carroccio A, Soresi M, Chiavetta M, La Blasca F, Compagnoni S, Giuliano A, Fayer F, Mandreucci F, Castellucci D, Seidita A, Affronti A, Florena AM, Mansueto P. Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity. Nutrients. 2021 Jun 8;13(6):1971. doi: 10.3390/nu13061971.
Mansueto P, Di Liberto D, Fayer F, Soresi M, Geraci G, Giannone AG, Seidita A, D'Alcamo A, La Blasca F, Lo Pizzo M, Florena AM, Dieli F, Carroccio A. TNF-alpha, IL-17, and IL-22 production in the rectal mucosa of nonceliac wheat sensitivity patients: role of adaptive immunity. Am J Physiol Gastrointest Liver Physiol. 2020 Sep 1;319(3):G281-G288. doi: 10.1152/ajpgi.00104.2020. Epub 2020 Jul 13.
A venous blood sample will be taken for each patient (1 dry tube and 1 EDTA tube). Blood samples will be stored at -80°C and subsequently used for DNA extraction and KIR genotyping by KIR SSO Genotyping Test (One Lambda, Thermo Fisher, Monza, Italy).
Antonio Carroccio, MD
Department of Internal Medicine, "Cervello" Hospital of Palermo, Italy
Marcello Ciaccio, MD
Institute of Clinical Biochemistry, University of Palermo, Italy
170 participants (actual enrollment reported by the registry).
First Submitted
July 11, 2022
First Posted
July 22, 2022
Study Start
November 1, 2022
Actual (reported)Malnutrition In Non-Celiac Wheat Sensitivity Patients
Contact the study team to confirm eligibility.
Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996.
Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24.
Santin I, Castellanos-Rubio A, Perez de Nanclares G, Vitoria JC, Castano L, Bilbao JR. Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4. Genes Immun. 2007 Mar;8(2):171-6. doi: 10.1038/sj.gene.6364367. Epub 2007 Jan 11.
Fernandez-Jimenez N, Santin I, Irastorza I, Plaza-Izurieta L, Castellanos-Rubio A, Vitoria JC, Bilbao JR. Upregulation of KIR3DL1 gene expression in intestinal mucosa in active celiac disease. Hum Immunol. 2011 Aug;72(8):617-20. doi: 10.1016/j.humimm.2011.04.008. Epub 2011 May 13.
Caggiari L, Toffoli G, De Re V, Orzes N, Spina M, De Zorzi M, Maiero S, Cannizzaro R, Canzonieri V. KIR/HLA combination associated with the risk of complications in celiac disease. Int J Biol Markers. 2011 Oct-Dec;26(4):221-8. doi: 10.5301/JBM.2011.8903.
Akar HH, Patiroglu T, Sevinc E, Aslan D, Okdemir D, Kurtoglu S. Contribution of KIR genes, HLA class I ligands, and KIR/HLA class I ligand combinations on the genetic predisposition to celiac disease and coexisting celiac disease and type 1 diabetes mellitus. Rev Esp Enferm Dig. 2015 Sep;107(9):547-53. doi: 10.17235/reed.2015.3817/2015.
Primary Completion
June 30, 2023
Actual (reported)Study Completion
September 30, 2023
Actual (reported)Last Updated
November 28, 2023
Record last verified: 2023-11
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