Coeliac Disease and Mast Cells.

Over the last decades, there has been an impressive progress in our understanding of coeliac disease pathogenesis and it has become clear that the disorder is the final result of complex interactions of environmental, genetic, and immunological factors. Coeliac disease is now considered a prototype of T-cell-mediated disease characterized by loss of tolerance to dietary gluten and the targeted killing of enterocytes by T-cell receptor αß intraepithelial lymphocytes. Accumulating evidence, however, indicates that the induction of a gluten-specific T helper-1 response must be preceded by the activation of the innate immune system. Mast cells are key players of the innate immune response and contribute to the pathogenesis of a multitude of diseases. Here, we review the results of studies aimed at investigating the role of mast cells in the pathogenesis of coeliac disease, showing that these cells increase in number during the progression of the disease and contribute to define a pro-inflammatory microenvironment.

Mast cells are associated with the onset and progression of celiac disease.

BACKGROUND: Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed. OBJECTIVE: We aimed at evaluating the role of MCs in the pathogenesis of CD. METHODS: Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration and MC distribution. Moreover, MC reactivity to gliadin and its peptides was characterized by using in vitro assays. RESULTS: Infiltrating MCs were associated with the severity of mucosal damage, and their numbers were increased in patients with higher Marsh scores. MCs were found to directly respond to nonimmunodominant gliadin fragments by releasing proinflammatory mediators. Immunohistochemical characterization of infiltrating MCs and the effects of gliadin peptides on intestinal MCs indicated an increase in proinflammatory MC function in advanced stages of the disease. This was also associated with increased neutrophil accumulation, the prevalence of M1 macrophages, and the severity of tissue damage. CONCLUSION: We provide a description of the progressive stages of CD, in which MCs are the hallmark of the inflammatory process. Thus the view of CD should be revised, and the contribution of MCs in the onset and progression of CD should be reconsidered in developing new therapeutic approaches.

The clinical spectrum of omega-5-gliadin allergy.

BACKGROUND: IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. AIMS: This study documents clinical manifestations in a large series of patients with sIgE to O5G. METHODS: A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. RESULTS: Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. CONCLUSION: WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Coeliac disease in Asians in a single centre in southern Derbyshire.

BACKGROUND: Coeliac disease affects adult Asians from north India, Pakistan and Bangladesh in the UK but how commonly this occurs is unknown. An audit of coeliac disease was therefore conducted in a well-defined area in southern Derbyshire. METHODS: All white and Asian patients with biopsy-confirmed coeliac disease diagnosed between 1958 and 2008 were identified. Population data from the Office of National Statistics allowed the calculation of prevalence. Presenting symptoms, adherence to a gluten-free diet and follow-up record were determined for Asians and compared with matched white patients. RESULTS: Among 1305 coeliac patients diagnosed between 1958 and 2008, 82 were Asian. Coeliac disease occurred significantly more frequently in Asian than white individuals and this could be attributed to the significantly higher prevalence in women 16 years and older and under 60 years of age. No Asian man over the age of 65 years was diagnosed with coeliac disease. Asians are more likely to present with anaemia and less likely to present with diarrhoea than white individuals. Asians are less likely to adhere to a strict gluten-free diet than white patients. CONCLUSIONS: This baseline audit indicates that increased efforts should be directed towards diagnosing coeliac disease in Asian men over the age of 65 years, in whom at present it is unrepresented. Strategies also need to be developed to help more Asian patients adhere strictly to the gluten-free diet.