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