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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non-Celiac Wheat Sensitivity

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-celiac Wheat Sensitivity Patients<br>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<br>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<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Celiac Wheat Sensitivity, Autoimmune diseases, Anti-nuclear antibodies, Celiac disease, Irritable bowel syndrome