Nutrition and Celiac Disease

Nutrition and Celiac Disease Raanan Shamir, MD 4th NNI Paediatric Nutrition Course Glion, Switzerland, July 2012 Learning objectives ™ What is Celi...
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Nutrition and Celiac Disease Raanan Shamir, MD

4th NNI Paediatric Nutrition Course Glion, Switzerland, July 2012

Learning objectives ™ What is Celiac Disease ™ Prolamines and their toxicity ™ Genes and toxicity ™ Treatment ™ Prevention

What is CD? New Definition 2012 “CD is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically (mainly HLA) susceptible individuals, characterized by the presence of variable combination of gluten-dependent clinical manifestations, CD specific antibodies, HLA DQ2 and DQ8 haplotypes and enteropathy” New guidelines for diagnosis. JPGN 2012

Clinical presentation

Clinical presentation, SCMCI 2000-2008 Short Stature

Anemia (IDA) 35%

30%

25%

20%

15%

10%

5%

Abdominal pain

0%

Mozer-Glassberg, et al. Digestion 2011

Epidemiology

DQ8

Genetic susceptibility

DQ2

Non HLA

Silent CD

Mucosal lesion

Potential CD Normal mucosa

Healthy individuals

Intestinal morphology

Celiac disease

Plos one, 2011

1984: Based on diagnosed cases, the estimated birth cohort incidence was 1.7:1000 Dahan S, et al. J Epidemiol Community Health 1984;38:58

2002: Blood bank donors study: 0.6% Shamir R, et al. Am J gastroemnterol 2002;97:2589-94

The biological properties of gluten

Wheat Protein

Gluten

Albumins Globulins 12%

8%

Gliadins Glutenins 40%

40%

Why are prolamines toxic?

Lancet 2003

Adapted from Cerf-Benussan, et al. JPGN 2003

Di Sabatino. Lancet 2009

Systematic review: Tolerable amounts of gluten for people with CD ™13 studies: ¾ 3 Randomized controlled, 1 cohort, 2 cross-over, 7 cross sectional: The amount of tolerable gluten varies among people with CD. Although there is no evidence to suggest a single definitive threshold, a daily gluten intake of < 10 mg is unlikely to cause significant histological abnormalities Akobeng and Thomas. Aliment Pharmacol Ther 2008

Taxonomy of major cereal grains

Oats

First evidence for non-toxicity of oats: Janatuinen EK, et al. N Engl J Med 1995;333:1075-6 Janatuinen EK, et al. Gut 2002;50:332-5

Oats and CD

Koskinen et al. JPGN 2009

™ 3 groups of oat cultivars reacting differently against moAb G12 could be distinguished: a group with considerable affinity, a group showing slight reactivity and a third with no detectable reactivity. ™ These differences may explain the different clinical responses observed in patients suffering from CD and open up a means to identify safe oat cultivars, which could be used to enrich a GFD

Comino I, et al. Gut 2011

What would you recommend? ™“If taken in limited quantities, oats are safe for most individuals with CD” ™These oats and oat products must fulfill the standards for a GFD ™Patients on oats containing diet should be monitored by their physician for any symptoms and for serology

Genetics DQ2, 95% of CD pts.

,20-40% of Controls DQ8, 5% of patients

In HLA risk genotype, at age 3. 4.5% are TTG+ and 3.5% are biopsy+ JPGN 2010;50:49-53

Impact of the HLA gene dose

Koning F. gastroenterology 2005;129:1294-1301

The multifactorial etiology of CD

Di Sabatino et al. Lancet 2009

Treatment ™Elimination of gluten from the diet (lifelong!) ¾ Usually a dramatic response (normalization of mucosa up to 6 months)

Compliance with GFD

Cranney et.al. Gastroenterology 2005

Gluten free diet (SCMCI 2000-2008)

Dig Dis Sci 2011

Zonulin inhibition? Probiotics Non HLA

PEP treatment

HLA

Peptide based vaccine

Modified from Lancet 2003

Polimer sequestering gluten

Transamidation with mTTG + amine donor

Complications ¾Infertility ¾Osteoporosis ¾Neuropathies ¾Autoimmune disorders ¾Malignancy ¾ End stage renal disease

¾ Low

birth weight ¾ Response to vaccines ¾ Sepsis ¾ Pancreatitis ¾ GERD ¾ Stroke

Can we Prevent Celiac Disease?

Ivarsson A et al. Acta Pædiatr 2000, Myleus A, et al. ESPGHAN 2007

JPGN 2009; 49:170– 176

™Duration of breast feeding ™Breast feeding during gluten introduction

Duration of breast feeding (+) Auricchio 1983 (n=505)

BF