Prospective Studies on Celiac Disease On the Coeliac Affection


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Prospective Studies on Celiac Disease


On the Coeliac Affection



Definition

  • Celiac disease is an autoimmune condition

  • Occurs in genetically susceptible individuals

    • DQ2 and/or DQ8 positive HLA haplotype is necessary but not sufficient
  • A unique autoimmune disorder because:

    • both the environmental trigger (gluten) and the autoantigen (tissue Transglutaminase) are known
    • elimination of the environmental trigger leads to a complete resolution of the disease


Pathogenesis

  • Genetic predisposition

  • Environmental triggers

    • Dietary
    • Non dietary?


Genetics

  • Several genes are involved

  • The most consistent genetic component depends on the presence of HLA-DQ (DQ2 and / or DQ8) genes

  • Other genes (not yet identified) account for 60 % of the inherited component of the disease

  • HLA-DQ2 and / or DQ8 genes are necessary (No DQ2/8, no Celiac Disease!) but not sufficient for the development of the disease





Dietary Factors



The Celiac Iceberg



Treatment Options



Treatment

  • Only treatment for celiac disease is a gluten-free diet (GFD)

    • Strict, lifelong diet
    • Avoid:
      • Wheat
      • Rye
      • Barley


Gluten-Containing Grains to Avoid



Sources of Gluten

  • OBVIOUS SOURCES

    • Bread
    • Bagels
    • Cakes
    • Cereal
    • Cookies
    • Pasta / noodles
    • Pastries / pies
    • Rolls


Sources of Gluten



Gluten-Free Grains and Starches



Other Items to Consider

  • Lipstick/Gloss/Balms

  • Mouthwash/Toothpaste

  • Play Dough

  • Stamp and Envelope Glues

  • Vitamin, Herbal, and

  • Mineral preparations

  • Prescription or OTC Medications



Dietary Adherence: A Common Problem

  • Only 50% of Americans with a chronic illness adhere to their treatment regimen including:

    • diet
    • exercise
    • medication
  • Dietary compliance can be the most difficult aspect of treatment



Health Beliefs of Adults with Celiac Disease

  • Survey of 100 people in Celiac Disease support group (Buffalo, NY)

    • Number of people who agreed with following statements:
      • “If I eat less gluten I will have less intestinal damage.” –51%
      • “I’ve lived this long eating gluten, how much will the gluten- free diet really help me now?” –33%
      • “My doctor should be the one to tell me when I need follow up testing.” –26%
      • “Scientist/doctors still haven’t proven that gluten really hurts them.” –16%


Barriers to Compliance

  • Ability to manage emotions – depression, anxiety

  • Ability to resist temptation – exercising restraint

  • Feelings of deprivation

  • Fear generated by

  • inaccurate information



Barriers to Compliance

  • Time pressure – time to plan, prepare food is longer

  • Planning – work required to plan meals

  • Competing priorities – family, job, etc.

  • Assessing gluten content in

  • foods/label reading

  • Eating out – avoidance, fear, difficult to ensure food is safe



  • Gluten and treatment of Celiac Disease:

  • How Much is Too Much?



The gluten microchallenge study



Investigating the dose-effect relationship the gluten microchallenge

  • CD patients on long-term, strict GFD

  • Perspective study design

  • While the GFD is maintained throughout the study-period, a given amount of gluten/gliadin is added to the diet

  • Clinical, serological and biopsy evaluation before and after the microchallenge

  • The background noise caused by possible gluten contamination of the GFD was minimized by inclusion of a control group





Why performinging a new microchallenge study

  • Need of investigating the effects of lower gluten doses

  • Need of prolonging the duration of the microchallenge

  • Need of a control group

  • Need of investigating gluten rather than gliadin



Gluten and Giadins

  • Gluten is the main proteic fraction in wheat (8-14 %);

  • The toxicity is mainly due to the gliadins (50 %), however glutenins also contribute to toxicity;

  • Daily intake of gluten in adults: ~ 15 g (Dautch data);

  • Daily consumption of flower for a typical GFD in celiac subjects: ~ 80 g;

  • 200 mg/Kg of gluten = 100 mg/Kg of gliadin = 100 ppm of gliadin (=2.5g of bread!)



The new microchallenge study

  • AIM

  • To evaluate the consequences of the protracted ingestion of minimal daily gluten intake (either 10 or 50 mg) in a group of adult celiacs on long-term treatment with the gluten-free diet (GFD)

  • TYPE OF STUDY

  • Multicentre, prospective, randomized, placebo-controlled, double-blind

  • STUDY PERIOD

  • Years 2001-2004

  • SPONSOR

  • Italian Celiac Society (AIC)



The “new” Italian microchallenge study

  • INCLUSION CRITERIA

  • Patients with biopsy-proven CD on a GFD for at least 2 years



The Italian microchallenge study Study-Design



The Italian microchallenge study Methods

  • Purified gluten was used for the microchallenge study (Amygluten 110, Tate & Lyle, UK)

  • Gluten- or lactose (placebo) containing capsules were centrally prepared

  • All laboratory tests were centrally performed

  • Monthly monitoring of adherence to the protocol

  • Measurement of gluten contamination in commercially available GF food by ELISA (Ridascreen Gliadin, R-Biopharm AG, Germany)

  • Serum AGA (ELISA) and anti-tTG (ELISA)

  • Small bowel biopsy and morphometry on 10 villi, IEL count (CD3+), ab IEL count

  • Control biopsies from non-celiac GE patients



Gluten content in commercially-available gluten free products in Italy where currently food labeling policies for gluten free products are set at 20 ppm



The Italian microchallenge study Subjects completing the study

















Tolerable daily intake of gluten and ppm of gluten in food for celiacs



Toxicity of gluten traces: the Italian study on gluten microchallenge




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