A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease.
ABSTRACT MICA molecules interact with the NKG2D-activating receptor on human NK and CD8 T cells. We investigated the participation of the MICA/NKG2D pathway in the destruction of intestinal epithelium by intraepithelial T lymphocytes (IEL) in Celiac disease and its premalignant complication, refractory sprue. We show that MICA is strongly expressed at epithelial cell surface in patients with active disease and is induced by gliadin or its p31-49 derived peptide upon in vitro challenge, an effect relayed by IL-15. This triggers direct activation and costimulation of IEL through engagement of NKG2D, leading to an innate-like cytotoxicity toward epithelial targets and enhanced TCR-dependent CD8 T cell-mediated adaptive response. Villous atrophy in Celiac disease might thus be ascribed to an IEL-mediated damage to enterocytes involving NKG2D/MICA interaction after gliadin-induced expression of MICA on gut epithelium. This supports a key role for MIC/NKG2D in the activation of intraepithelial immunity in response to danger.
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ABSTRACT: Despite ongoing progresses of IVF techniques, biomarkers predicting their outcome prior to IVF initiation are lacking. We investigated whether serum levels of the stress-inducible soluble major histocompatibility complex Class I chain-related molecule, MICA, (sMIC), a regulator of cellular immunity, can be predictive of implantation or pregnancy failure after IVF. sMIC serum levels, evaluated during the follicular phase of the cycle preceding in vitro fertilization, in a cohort of 170 infertile women with 22.3% IVF success rate were analyzed in association with implantation/pregnancy failure or live birth outcomes after IVF. sMIC serum levels, detected in 38% of all women undergoing IVF, were shown to be predictive both of implantation failure (> or = 2.45 ng/ml cut off, odds ratio (OR) = 4.6; 95% confidence interval (CI) = 1.08 - 19.79; P = 0.031) and successful pregnancy (< 2.45 ng/ml, OR = 13.8; 95% CI = 2.03-118.3; P = 0.002). When successful implantation occurred, sMIC levels > 3.2 ng/ml were predictive of spontaneous abortion (OR = 35; 95% CI = 1.74-703; P = 0.026). sMIC is thus to be considered as a novel blood biomarker which, when quantified prior to initiation of IVF, anticipates chances for infertile women to give birth to a viable baby. Considering medical and psychological cost of IVF, this non-invasive assay may thus contribute to better counseling, treatment and care of infertile couples prior to IVF.Human Reproduction 09/2007; 22(8):2261-6. DOI:10.1093/humrep/dem157 · 4.59 Impact Factor
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ABSTRACT: Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of refractory coeliac disease type II RCDII and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. The aim of this study was to gain further insight in the origin and characteristics of aberrant IELs by analysing T-cell receptor (TCR) rearrangements, and by immunophenotypic analysis of aberrant IELs. Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed for the presence of TCR delta, gamma, and beta rearrangements. In addition, IELs isolated from biopsies derived from RCDII patients were phenotypically analysed. Aberrant IELs showed an upregulated expression of granzyme B and decreased expression of PCNA. TCR rearrangements in the aberrant IEL population in biopsies of RCDII patients were heterogenic, which is most likely due to a variation in maturity. Similarly, RCDII cell lines displayed a heterogenic TCR rearrangement pattern. Aberrant IELs originate from deranged immature T lymphocytes and display clear differentiation to a cytotoxic phenotype. Aberrant IELs displayed different stages of maturity between RCDII patients, of which only the patients harbouring the most mature aberrant IEL population developed an EATL.Molecular Immunology 02/2012; 50(4):262-70. DOI:10.1016/j.molimm.2012.01.014 · 3.00 Impact Factor
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ABSTRACT: A gluten-free diet (GFD) is currently the only available therapy for coeliac disease (CD). We aim to review the literature on the GFD, the gluten content in naturally gluten-free (GF) and commercially available GF food, standards and legislation concerning the gluten content of foods, and the vitamins and mineral content of a GFD. We carried out a PubMed search for the following terms: Gluten, GFD and food, education, vitamins, minerals, calcium, Codex wheat starch and oats. Relevant papers were reviewed and for each topic a consensus among the authors was obtained. Patients with CD should avoid gluten and maintain a balanced diet to ensure an adequate intake of nutrients, vitamins, fibre and calcium. A GFD improves symptoms in most patients with CD. The practicalities of this however, are difficult, as (i) many processed foods are contaminated with gluten, (ii) staple GF foods are not widely available, and (iii) the GF substitutes are often expensive. Furthermore, (iv) the restrictions of the diet may adversely affect social interactions and quality of life. The inclusion of oats and wheat starch in the diet remains controversial.04/2015; 3(2):121-35. DOI:10.1177/2050640614559263