Autoimmune Diseases And Serum Anti-Nuclear Antibodies Positivity In Non-Celiac Wheat Sensitivity Patients

NCT02248545 | Completed

• 1 other identifier: ACPM06
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

Celiac disease (CD) is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in genetically predisposed patients and resolves with exclusion of gluten from the diet. Patients with CD show circulating autoantibodies (anti-transglutaminase, anti-tTG) and suffer from the destruction of a specific tissue cell type (the enterocytes) by CD8+ T cells. Furthermore, other autoimmune diseases have been reported in association to CD in 20-30% of the cases. In the last few year, a new clinical entity emerged, which seems include patients who consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named "Non-Celiac Gluten Sensitivity" (6), but, in a recent paper, the investigators suggested the term "Non-Celiac Wheat Sensitivity" (NCWS), since, to date, it is not known what component of wheat really causes the symptoms. The doubt areas about the NCWS regard also its pathogenesis as, despite some papers evidenced an intestinal immunologic activation, others excluded it. To explore the presence of autoimmunity in NCWS, the investigators evaluated: a) the frequency of autoimmune diseases and b) the frequency of serum anti-nuclear antibodies (ANA) positivity in newly diagnosed NCWS, compared to CD patients.

Conditions

Non-Celiac Wheat Sensitivity

Keywords

Non-Celiac Wheat Sensitivity; Autoimmune diseases; Anti-nuclear antibodies; Celiac disease; Irritable bowel syndrome

Outcome Measures

Primary Outcomes (1)

• Organ- and non-organ specific autoantibodies

  We evaluated, by ELISA and Immunofluorescence, organ- and non-organ specific autoantibodies, i.e. Anti-Nuclear Antibodies (ANA) IgG, anti double-strand (anti-ds) DNA IgG Antibodies, Anti-Mitochondrial Antibodies (AMA), Liver Kidney Microsome (LKM) IgG Antibodies, Anti-Smooth Muscle Antibodies (ASMA) IgG, anti-Sjogren's Syndrome antigen A (anti-SSA) IgG Antibodies, anti-Sjogren's Syndrome antigen B (anti-SSB) IgG Antibodies, anti-Smith (anti-Sm) IgG Antibodies, anti-ThyroPerOxidase (anti-TPO) IgG Antibodies, anti-ThyroGlobulin (anti-TG) IgG Antibodies, anti-Glutamic Acid Decarboxylase (anti-GAD) IgG Antobodies, and Islet Cell Antibodies (ICA) IgG.

  At first visit

Secondary Outcomes (1)

• Questionnaire for autoimmunity.

  At first visit

Study Arms (3)

Non-celiac Wheat Sensitivity Patients

Consecutive adult patients with irritable bowel syndrome (IBS)-like clinical presentation, according to Rome II criteria, and a definitive diagnosis of NCWS.

Celiac Disease Patients

Celiac disease adult patients, sex- and age-matched, diagnosed according to standard criteria, during the same study period, chosen at random and enrolled as first control group.

Irritable Bowel Syndrome Patients

Irritable Bowel Syndrome adult patients, sex- and age-matched, diagnosed according to Rome II criteria, and unrelated to NCWS or other food "intolerance", during the same study period, chosen at random and enrolled as second control group.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study included consecutive adult patients with irritable bowel syndrome (IBS)-like clinical presentation, according to Rome II criteria, and a definitive diagnosis of NCWS, referred at the Internal Medicine Department of the University Hospital of Palermo, Italy, and at the Internal Medicine Department of the Hospital of Sciacca, Agrigento, Italy, between July 2011 and July 2013.

You may qualify if:

• To diagnose NCWS the recently proposed criteria were adopted. All the patients met the following criteria
• negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) IgA and IgG antibodies
• absence of intestinal villous atrophy
• negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or serum specific IgE detection)
• resolution of the IBS symptoms on standard elimination diet, excluding wheat, cow's milk, egg, tomato, chocolate, and other self-reported food(s) causing symptoms
• symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge. As we previously described in other studies, DBPC cow's milk protein challenge and other "open" food challenges were performed too.
• age \>18 years
• follow-up duration longer than six months after the initial diagnosis
• at least two outpatient visits during the follow-up period.

You may not qualify if:

• positive EmA in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa
• other "organic" gastrointestinal disorders
• nervous system disease and/or major psychiatric disorder
• physical impairment limiting physical activity
• menopause
• steroid and sex steroid therapy, hormone replacement therapy or ovariectomy.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (3)

Internal Medicine Department of the Hospital of Sciacca (Agrigento)

Sciacca, Agrigento, 92019, Italy

Location

Gastroenterology Unit of the "Civico" Hospital of Palermo

Palermo, Palermo, 90100, Italy

Location

Internal Medicine Department of the University Hospital of Palermo

Palermo, Palermo, 90127, Italy

Location

Related Publications (8)

• Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013 May;108(5):656-76; quiz 677. doi: 10.1038/ajg.2013.79. Epub 2013 Apr 23.

  PMID: 23609613 RESULT

• Sollid LM, Jabri B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev Immunol. 2013 Apr;13(4):294-302. doi: 10.1038/nri3407. Epub 2013 Mar 15.

  PMID: 23493116 RESULT

• Sategna Guidetti C, Solerio E, Scaglione N, Aimo G, Mengozzi G. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut. 2001 Oct;49(4):502-5. doi: 10.1136/gut.49.4.502.

  PMID: 11559646 RESULT

• Biagi F, Pezzimenti D, Campanella J, Corazza GR. Gluten exposure and risk of autoimmune disorders. Gut. 2002 Jul;51(1):140-1. doi: 10.1136/gut.51.1.140-a. No abstract available.

  PMID: 12077109 RESULT

• Verdu EF, Armstrong D, Murray JA. Between celiac disease and irritable bowel syndrome: the "no man's land" of gluten sensitivity. Am J Gastroenterol. 2009 Jun;104(6):1587-94. doi: 10.1038/ajg.2009.188.

  PMID: 19455131 RESULT

• Catassi C, Bai JC, Bonaz B, Bouma G, Calabro A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vecsei A, Volta U, Zevallos V, Sapone A, Fasano A. Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders. Nutrients. 2013 Sep 26;5(10):3839-53. doi: 10.3390/nu5103839.

  PMID: 24077239 RESULT

• Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.

  PMID: 24275240 RESULT

• Mansueto P, Soresi M, Candore G, Garlisi C, Fayer F, Gambino CM, La Blasca F, Seidita A, D'Alcamo A, Lo Sasso B, Florena AM, Geraci G, Caio G, Volta U, De Giorgio R, Ciaccio M, Carroccio A. Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity. Am J Gastroenterol. 2021 May 1;116(5):1015-1023. doi: 10.14309/ajg.0000000000000919.

  PMID: 33009065 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Autoimmune Diseases; Celiac Disease; Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Immune System Diseases; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Colonic Diseases, Functional; Colonic Diseases

Study Officials

• Antonio Carroccio, MD, PhD

  Internal Medicine Department of the Hospital of Sciacca (Agrigento)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 20, 2014
• First Posted: September 25, 2014
• Study Start: July 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: June 1, 2014
• Last Updated: September 25, 2014

Record last verified: 2014-09

Locations

IT (3)