To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD).
Caecal biopsies were ...collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grade inflammation was evaluated by counting cells, including intraepithelial lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and protein expression of tumour necrosis factor (TNF)-α in biopsies and culture supernatants.
IBS-like symptoms were present in 35.4 and 38% of CD and UC patients, respectively. Paracellular permeability was significantly increased in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01, respectively). Significantly lower expression of ZO-1 and α-catenin was detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-α were significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS.
In quiescent IBD, IBS-like symptoms related to persistent subclinical inflammation associated with increased colonic paracellular permeability. A persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects associated with abdominal pain in quiescent IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered in quiescent IBD with IBS-like symptoms.
Vitiligo is an autoimmune skin disorder characterized by loss of melanocytes. Protease-mediated disruption of junctions between keratinocytes and/or keratinocyte intrinsic dysfunction may directly ...contribute to melanocyte loss. House dust mite (HDM), an environmental allergen with potent protease activity, contributes to respiratory and gut disease but also to atopic dermatitis and rosacea.
To verify if HDM can contribute to melanocyte detachment in vitiligo and if so, by which mechanism(s).
Using primary human keratinocytes, human skin biopsies from healthy and vitiligo patients, and 3D reconstructed human epidermis, we studied the effect of HDM on cutaneous immunity, tight and adherent junction expression and melanocyte detachment.
HDM increased keratinocyte production of vitiligo-associated cytokines and chemokines and increased expression of TLR-4. This was associated with increased in situ MMP-9 activity, reduced cutaneous expression of adherent protein E-cadherin, increased soluble E-cadherin in culture supernatant and significantly increased number of supra-basal melanocytes in the skin. This effect was dose-dependent and driven by cysteine protease Der p1 and MMP-9. Selective MMP-9 inhibitor, Ab142180 restored E-cadherin expression and inhibited HDM-induced melanocyte detachment. Keratinocytes from vitiligo patients were more sensitive to HDM-induced changes than healthy keratinocytes. All results were confirmed in 3D model of healthy skin and in human skin biopsies.
Our results highlight that environmental mite may act as an external source of PAMPs in vitiligo and topical MMP-9 inhibitors may be useful therapeutic targets. Whether HDM contributes to onset of flares in vitiligo remains to be tested in carefully controlled trials.
Le rôle des réactions immuno-allergiques aux aliments au cours du syndrome de l’intestin irritable (SII) reste controversé, en raison d’une symptomatologie peu spécifique et des méthodes ...diagnostiques limitées par l’accessibilité difficile du tube intestinal. Dans la pratique clinique, les manifestations au niveau du tractus gastro-intestinal des allergies alimentaires sont difficiles à évaluer et à les différencier des plaintes à expression gastro-intestinale d’autre origine. Les hypothèses physiopathologiques concernant l’hypersensibilité allergique aux aliments reposent sur des mécanismes immunologiques immédiats (IgE et non IgE) et retardés, incluant les mastocytes et les éosinophiles. Les concepts physiopathologiques récents dans le SII suggèrent l’existence d’altérations de l’intégrité de la barrière épithéliale intestinale qui favoriseraient une présentation accrue d’antigènes luminaux, le développement et le maintien d’une activation définie de « bas grade » de l’immunité muqueuse et du système nerveux entérique, potentiellement à l’origine des troubles de la motricité/sensibilité et des douleurs digestives. Les tests diagnostiques utilisés en pratique clinique pour objectiver les réactions aux aliments rapportées par les patients (tests cutanés et IgE spécifiques sériques) sont souvent négatifs, comme le test de provocation par voie orale. Des manifestations d’atopie (rhinite, dermatite, asthme) semblent être le terrain favorisant le SII, au moins dans le sous-groupe de patients qui rapportent des symptômes cliniques après l’ingestion de certains aliments.
The role of immuno-allergic reactions to food in patients with irritable bowel syndrome (IBS) remains controversial because of non-specific symptoms and of diagnostic methods limited by difficult accessibility to the gut. In clinical practice, the manifestations of food hypersensitivity in the gastro-intestinal tract are difficult to assess and to differentiate from digestive symptoms due to other causes. Pathophysiological hypotheses based on immunological mechanisms of immediate hypersensitivity (IgE and non IgE) and of delayed hypersensitivity, including mast cells and eosinophils, have been proposed. Recent pathophysiological concepts concerning IBS suggest the existence of alterations in the integrity of the intestinal epithelial barrier that would promote increased presentation of luminal antigens, with the development and maintenance of “low grade” mucosal inflammation with involvement of the enteric nervous system, potentially being the origin of these sensitive motility disorders and the abdominal pain. The diagnostic tests used in clinical practice (skin tests and specific IgE serum) to identify the source of self-perceived reactions to food reported by patients are often negative, as are oral provocation tests. Classic manifestations of atopy (rhinitis, dermatitis, asthma) seem to be the background favoring IBS, at least in the subgroup of patients reporting clinical symptoms after ingestion of certain foods.
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