Non-responsive coeliac disease has persistent symptoms and enteropathy that do not respond after 6 – 12 months on a self-reported gluten-free diet . 19
Refractory coeliac disease has persistent or recurrent symptoms and villous atrophy on duodenal biopsy , despite strict adherence to a gluten-free diet for at least 12 months . 19
Alongside genetic predisposition and gluten exposure , loss of intestinal barrier function , a pro-inflammatory innate immune response triggered by gluten and an imbalanced gut microbiome all appear to be important elements of the autoimmune response in coeliac disease . 17
Some 27 % of people with coeliac disease present with classical symptoms of diarrhoea , weight loss and malabsorption but 21 % have no symptoms and 52 % present with non-classical symptoms . 17 Women are often diagnosed at an earlier age than men and present more often with constipation , bloating , and iron-deficiency anaemia . 1
Complications are rare with coeliac disease – occurring in about 1 % of people diagnosed – but can include hyposplenism , intestinal lymphoma and ulcerative jejunoileitis . 17
Incidence and prevalence In western countries , the prevalence of coeliac disease is around 1 % with serological screening of the general population and 0.6 % in histologically confirmed cases ; however , it is believed to be underdiagnosed 19 and only 36 % of people with the condition are currently clinically diagnosed . 20 It affects all age groups , including the elderly , with more than 70 % of new cases diagnosed in people over 20 years of age . Coeliac disease is diagnosed more frequently in women than in men . A metaanalysis of 50 studies found that the global pooled female incidence was 17.4 per 100,000 person-years , compared with 7.8 in males . 21
In common with other autoimmune diseases , coeliac disease has a strong hereditary component . There is high familial recurrence ( 10 %– 15 %) and a concordance ( 75 %– 80 %) among monozygotic twins . 17
Genetic susceptibility Coeliac disease occurs in genetically susceptible individuals who have HLA-DQ8 or HLADQ2 . Approximately 25 %– 35 % of the general population has HLA-DQ2 / DQ8 but only 3 % of these will go on to develop coeliac disease . 17
Intestinal microbial flora Studies have shown an association between coeliac disease and changes in the composition of the gut microbiome . However , further investigations to define if , and how , the composition of the microbiota and metabolomic profiles might influence the onset of coeliac disease in genetically susceptible subjects are required . 17
Environmental factors In coeliac disease , exposure to dietary gluten causes the immune system to attack host tissues ( in this case , the small bowel mucosa ), damaging the intestinal villi in the small bowel . The consequent
Current and future research will further improve understanding and point the way to new options for treatment and / or prevention of these debilitating conditions . reduction in absorbing surface can lead to malabsorption of nutrients .
Key components of gluten are the gliadins , which are complex proteins rich in prolines and glutamines and which can only be digested partially by intestinal enzymes . The resultant product of this partial digestion triggers host responses ( such as increased gut permeability and innate and adaptive immune responses ). 17 Moreover , there is evidence that gluten can also cross the intestinal barrier once tolerance to gluten has been broken . 17
Immune dysregulation tTG is believed to play a key role in the pathogenesis of coeliac disease . It enhances the immunostimulatory effect of gluten and acts as a target autoantigen in the immune response . Gliadin peptides are excellent substrates for tTG , and the resulting deamidated peptides have a much greater affinity for HLA-DQ2 and HLA-DQ8 . 22
Conclusions Current thinking suggests that the main autoimmune gastrointestinal diseases involve an interplay between genetic predisposition , environmental factors and the gut microbiome , thereby resulting in inflammatory disease and gut malfunction . Current and future research will further improve understanding of these factors and point the way to new options for treatment and / or prevention of these debilitating conditions .
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