Please select the eligibility criteria that correspond to the clinical trial below.
Title: Lymphocytic Enteritis and Suspected Coeliac Disease: Double-blind Gluten vs Placebo Rechallenge
Brief Summary: Patients with lymphocytic enteritis (LE), HLA-DQ2/8+, negative celiac serology and clinical and histological response to a gluten-free diet (GFD) do not fulfil the diagnostic criteria of coeliac disease (CoD). At present it remains unclear whether they suffer from coeliac gluten sensitivity (CGS) or non-coeliac gluten sensitivity (NCGS). There are specific tissue markers of CoD such as anti-transglutaminase deposits (tTG) and intraepithelial lymphocytes expressing T-cell receptor (TCR) gamma/delta+.

Aim: To demonstrate the existence of CGS in these patients despite having negative celiac serology.

Methods: Double-blind randomized clinical trial of gluten vs placebo rechallenge for 6 months in patients with LE on a GFD. Inclusion criteria: \>18 years, initial presentation with GI symptoms, HLA-DQ2/8+, negative celiac serology, good clinical and histological response to GFD. Patients were randomised to gluten (20 g/day) and placebo (maltrodextrin) (identical powder sachets mixed with meals). Clinical symptoms were analysed using visual analogue scales. Quality of life (GIQLI), adherence to diet, serology, and histological changes including gamma/delta+ IEL and tTG deposits were evaluated.


Options:
A: Inclusion Criteria:

* male or female, aged 18-70, who believe they experience non-coeliac gluten sensitivity

Exclusion Criteria:

* Medical exclusion criteria

  * Coeliac Disease
  * Wheat allergy
  * Dermatitis Herpetiformis
  * Gastrointestinal disorders: Small Intestinal Bowel Overgrowth (SIBO), Crohn's disease , Ulcerative Colitis, Inflammatory Bowel Disease (IBD)
  * History of gastrointestinal surgery/procedure over the last 3 years
  * Kidney disease
  * Hepatic disease
  * Active cancer
  * Severe cardiovascular disease
  * Addiction to any substances
  * Breastfeeding/ Pregnancy

Volunteers with poorly controlled psychiatric disease or those unable to give written informed consent will also be excluded.

Medication exclusion criteria

* Medications for treatment of heartburn, dyspepsia, indigestion, bloating etc. e.g. gastrokinetics or prokinetics, antacids, laxatives
* Digestive enzymes
B: Inclusion Criteria:

* first degree relatives of CD patients
* subjects with autoimmune disease tested negative for serum anti-tTG but positive for CD related HLA DQ2 or DQ8
* symptomatic subjects (genetically predisposed to gluten intolerance) tested negative for CD related autoantibodies and with apparently normal intestinal mucosa.

Exclusion criteria:

- None
C: Inclusion Criteria:

1. Giving written informed consent
2. Patients with age ≥18 years
3. Histological diagnosis confirmed of lymphocytic enteritis (LE)
4. Celiac genetic study (HLA-DQ2 and /or HLA-DQ8 positive)
5. Negative serology of celiac disease
6. Previous complete clinical and histological response to gluten-free diet
7. Initial (at diagnosis) GI symptoms with or without extraintestinal manifestations.
8. No previous studies on both IEL cytometric pattern and anti-TG2 IgA subepithelial deposits.

Exclusion Criteria:

1. Patients who are unable to adhere to the study visit schedule and other protocol requirements according to the investigator.
2. Participation in a clinical trial in the last 30 days, simultaneous participation in a trial or prior participation in this study.
3. Previous diagnosis with gluten-sensitive enteropathy with villous atrophy and positive serology.
4. Patients with LE and initial response to gluten free diet but that at the time of inclusion are on a normal gluten-containing diet.
5. Severe co-morbidities.
6. Drug or alcohol abuse.
7. Pregnancy or breast-feeding.

At the initial diagnosis, other LE aetiologies, like non-steroidal anti-inflammatory drugs intake, parasitic infection, and Helicobacter pylori infection, were appropriately ruled out.
D: Inclusion Criteria:

* Positive endomysial antibodies
* Adults

Exclusion Criteria:

* Previous celiac disease diagnosis
* Significant clinical symptoms
* Suspicion of any serious celiac disease-associated complication
* Suspected or diagnosed severe illness other than celiac disease
* Consuming oral corticosteroids or immune suppressants
* Marked laboratory abnormalities

Answer: C