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

Non-Celiac Wheat Sensitivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02248545
• Other study ID #: ACPM06
• Status: Completed
• Phase: N/A
• First received: September 20, 2014
• Last updated: September 24, 2014
• Start date: July 2011
• Est. completion date: June 2014

Study information

• Verified date: September 2014
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministero dell'Istruzione, dell'Università e della Ricerca.
• Study type: Observational

Clinical Trial 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.

Description:

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. Although CD is not surely placed among the autoimmune diseases, 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 linked NCWS to the dietary FODMAPs (Fermentable Oligo-di and Mono-saccharides, And Polyols) load, thus excluding an immunologic involvement in the NCWS. To explore the presence of autoimmunity in NCWS, in the present study the investigators evaluated: a) the frequency of autoimmune diseases and b) the frequency of serum anti-nuclear antibodies (ANA) positivity in newly diagnosed NCWS and CD patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: June 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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.

• Additional inclusion criteria were:

• age >18 years

• follow-up duration longer than six months after the initial diagnosis

• at least two outpatient visits during the follow-up period.

Exclusion Criteria:

• positive EmA in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa

• self-exclusion of wheat from the diet and refusal to reintroduce it, before entering the study

• 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.

Study Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Autoimmune Diseases
• Non-Celiac Wheat Sensitivity

Locations

Country	Name	City	State
Italy	Gastroenterology Unit of the "Civico" Hospital of Palermo	Palermo
Italy	Internal Medicine Department of the University Hospital of Palermo	Palermo
Italy	Internal Medicine Department of the Hospital of Sciacca (Agrigento)	Sciacca	Agrigento

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (7)

Biagi F, Pezzimenti D, Campanella J, Corazza GR. Gluten exposure and risk of autoimmune disorders. Gut. 2002 Jul;51(1):140-1. — View Citation

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. — View Citation

Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò 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, Vécsei A, Volta U, — View Citation

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 201 — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Questionnaire for autoimmunity.	The presence of autoimmune disorders was evaluated by a structured questionnaire, with the assistance of ad hoc-trained personnel, and review of patient' clinical records. The presence of one of the following diseases was looked for in all subjects: connective tissue diseases, autoimmune endocrinological diseases, autoimmune hepatitis, primary biliary cirrhosis, epilepsy with cerebral calcification, unexplained cerebellar ataxia, alopecia, psoriasis, dermatitis herpetiform, atrophic autoimmune gastritis, and immune anemia, neutropenia, or thrombocytopenia. The hospital records of all patients diagnosed for an autoimmune disorder were thoroughly examined to verify whether the recognized diagnostic criteria for each disorder had been fulfilled, together with age at diagnosis of the diseases and treatment received.	At first visit	No