Wheat-induced disorders besides coeliac disease: non coeliac gluten intolerance (gluten-sensitivity) and wheat allergy

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1 Wheat-induced disorders besides coeliac disease: non coeliac gluten intolerance (gluten-sensitivity) and wheat allergy Katri Kaukinen University of Tampere and Tampere University Hospital Finland

2 Gluten-sensitive diarrhea without atrophy Cooper et al. Gastroenterology 1980;79:801-6 IELs cells/mm n=9 n=8 n=17 Responders Non-responders Controls gluten gfd Only 3 responders had celiac type HLA B8

3 Self-reported abdominal symptoms after ingestion of cereals n =93 Celiac disease n=8 (9%) Celiac disease excuded n=85 (91%) Villous atrophy 100% 0% Lymphosytosis CD3+ 100% 9% Increased γδ+ IELs 100% 19% Serum TG2-ab+ 100% 0% Serum AGA+ 83% 46% HLADQ2/8 100% 51% Cereal allergy 9% Dg? 82% Kaukinen et al Scand J Gastroenterol 200;35:942-6

4 AGA+ without celiac disease in different conditions IBD (Tursi et al Inflamm Bowel Dis 2005) Arthritis (Pellegrini et al Clin Exp Reymatol 1991) Psoriasis (Michaelsson et al Br Clin Dermatol 2000) Sjögren s syndrome (Iltanen et al Am J Gas 1999) Schitzophrenia (Samaroo et al Schizophr Res 2009) Mania (Dickerson et al Psychiatr Res 2012) Autism (Vojdani et al Nutr Neurosci 2004) Autoimmune liver disorders (Volta et al Lancet 1998) (Neurological disorders: gluten ataxia, gluten neuropathy etc)

5 AGA-positivity in older population AGA-positivity without CD was related to: -Rheumatoid arthritis -Depression -Osteopenia/osteoporosis No association with e.g: -Neurological diseses -Malignancies -Diabetes, allergic and cardiovascular diseases Ruuskanen et al Scand J Gastroenterol 2010;45:

6 Persistent AGA positivity in 81% of those initially positive Only one (2.8%) had CD 54% showed signs of inflammation More previous and current gastrointestinal symptoms

7 Jejunal fluid celiac-type antibody pattern as a marker of gluten-sensitive disorder without atrophy IgA and IgM antibodies to gliadin, ovalbumin and β-lactoglobulin n=7 Jejunal celiac-type antibody pattern + - no villous atrophy - IELs increased in 5 GFD 1 week- 6 months Diarrhea resolved in 5, mouth ulcers improved in 1 No effect on symptoms in 2 Follow-up biopsy: IELs decresed in 3, no change in 2 Arranz et al. Gastroenterology 1993;104:

8 Diarrhea-dominant IBS and duodenal celiac-type antibody pattern IgA and IgM antibodies to gliadin, transglutaminase, ovalbumin and β-lactoglobulin N=102 d-ibs serum ab 0%, duodenal aspirate ab 30% n=26 d-ibs+ GFD 6 months Stool frequency decreased in duodenal celiac-type antibody pattern +, HLA DQ2+ patient Wahnschaffe et al. Gastroenterology 2001;121:

9 Diarrhea-dominant IBS and serum AGA N=145 d-ibs serum AGA/TG2-ab IgG 36%, IgA 3% n=41 d-ibs+ GFD 6 months Positive IgG AGA, HLA DQ2 > symptom response in 60% Negative IgG AGA, HLA DQ2 > symptom response in 12% Wahnschaffe et al. Clin Gastroenterol Hepatol 2007;5:844-50

10 Randomized, dobble-blind intervention study Biesiekierski et al Am J Gastroenterol 2011

11 BMC Medicine, 2012;10:13

12 Prevalence of non-cd gluten-sensitivity estimation 6% (based on Baltimore experiences) BMC Medicine, 2012;10:13

13 Gluten sensitivity: symptoms similar to those in CD or wheat allergy Abdominal pain 68-77% Diarrhea 33-40% Anemia 15-20% Headache 32-35% Foggy mind 34-42% Eczema/rash 33-44% Fatigue 33-36% Joint pain 11-28% Depression 15-22% Numberness legs/arms 17-20% Sapone et al BMC Med 2012, Volta et al Nat Rev Gastroenterol Hepatol 2012

14 Non-CD gluten sensitivity CD excluded, EMA TGA negative Wheat allergy excluded Small bowel mucosal villi normal AGA may be positive Not restricted to HLA DQ2/8 CD/wheat allergy-type symptoms Symptoms recover on GFD and reapper again on gluten challenge (Double blind gluten challenge!)

15 Gluten sensitivity: Pathogenetic mechanisms different from celiac disease Innate immunity reactions?

16 Gluten sensitive subjects who do not have celiac disease or wheat allergy clearly exist however

17 Non-CD gluten-sensitivity: open questions Natural history? Transient? Permanent? Associated conditions? Prognosis? Prevalence? Pathogenesis? In Children/ in adults? Reliable biomarkers? Harmful component in wheat: gluten or other?