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Grossi A.,Bambino Gesu Childrens Hospital IRCCS | Crino A.,Bambino Gesu Childrens Hospital IRCCS | Luciano R.,Research Laboratories | Lombardo A.,Cytogenetics and Molecular Genetics Unit | And 2 more authors.
Italian Journal of Pediatrics | Year: 2013

Background: Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods. Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined. Results: Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto's thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves' disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0-9.9, 10-19.9 and 20-29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (χ§ssup§2§ esup§-test p > 0.05).Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (χ§ssup§2§esup§-test p = 0.0173).When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was statistically higher in the X isochromosome group (Fisher exact test p = 0.0315). Conclusions: Our data confirm a high frequency of thyroid autoimmunity in Italian Turner patients. Patients with X isochromosome are more prone to develop thyroid autoimmunity. Further, an early assay of autoantibodies and monitoring thyroid hormones is fundamental for detecting hypothyroidism earlier and start adequate replacement therapy. © 2013 Grossi et al.; licensee BioMed Central Ltd. Source


Fattore A.D.,Regenerative Medicine | Luciano R.,Regenerative Medicine | Pascucci L.,University of Perugia | Giorda E.,Immunology Unit | And 3 more authors.
Cell Transplantation | Year: 2015

The immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. We have recently shown that the immunosuppressive effects of MSCs on B lymphocytes in peripheral blood mononuclear cell (PBMC) culture can be reproduced by extracellular vesicles (EVs) isolated from MSC culture supernatants. Here we investigated the effect of bone marrow-derived MSC-EVs on T cells on PBMC cultures stimulated with anti-CD3/CD28 beads. Stimulation increased the number of proliferating CD3+ cells as well as of regulatory T cells (Tregs). Coculture with MSCs inhibited the proliferation of CD3+ cells, with no significant changes in apoptosis. Addition of MSC-EVs to PBMCs did not affect proliferation of CD3+ cells, but induced the apoptosis of CD3+ cells and of the CD4+ subpopulation and increased the roliferation and the apoptosis of Tregs. Moreover, MSC-EV treatment increased the Treg/Teff ratio and the immunosuppressive cytokine IL-10 concentration in culture medium. The activity of indoleamine 2,3-dioxygenase (IDO), an established mediator of MSC immunosuppressive effects, was increased in supernatants of PBMCs cocultured with MSCs, but was not affected by the presence of MSC-EVs. MSC-EVs demonstrate immunomodulatory effects on T cells in vitro. However, these effects and the underlying mechanisms appear to be different from those exhibited by their cells of origin. © 2015 Cognizant Comm. Corp. Source


Fierabracci A.,Autoimmunity Laboratory | Lazzari L.,Cell Factory Fondazione | Parolini O.,Centro Of Ricerca E Menni
Expert Opinion on Biological Therapy | Year: 2015

In recent years, multiple studies have investigated the biology and clinical applications of mesenchymal stem cells (MSCs), trying to define their markers, and elucidate their effects in animal models. MSCs are available from different tissues, and the use of placental-derived MSCs (PMSCs) for treating a variety of disorders is on the forefront. Herein, we discuss the most recent findings regarding the standardization of their isolation procedure and phenotype, along with advantages and limitations of their use. We also discuss the safety of the placental cell products, including the issue of senescence and mutagenesis of PMSCs, and efficacy from preclinical studies. © 2015 Informa UK, Ltd. Source


Autoimmune diseases are a heterogeneous group of disorders affecting different organs and tissues. New tools, such as genome-wide association studies, have provided evidence for new susceptibility loci and candidate genes in the disease process including common susceptibility genes involved in the immunological synapse and T cell activation. Close linkages have been found in a number of diseases, including ankylosing spondylitis, multiple sclerosis, Crohn's disease and insulin-dependent diabetes mellitus (Type 1 diabetes mellitus). Evidence for some association with Type 1 diabetes was previously found in the region containing 5q15/. ERAP1 (endoplasmic reticulum aminopeptidase 1) (rs30187, ARTS1).Recent data suggest that in eukaryotic cells in addition to the ubiquitin/proteasome system another proteolytic pathway may have a significant role in the autoimmunity process, i.e. the autophagic pathway which constitutes the principal regulated catabolic process mediated by lysosomes. Autophagy could play a role in MHC class I and class II self-antigen presentation at the basis of the autoimmunity process. Furthermore cross-talk among different proteolytic pathways was recently highlighted i.e. components processed in the ubiquitin/proteasome system possibly engaged in autophagic pathways.T1D is an autoimmune disease characterised by the destruction of pancreatic beta cells by autoreactive T cells. Immunological abnormalities can precede months to years the initial symptoms and clinical diagnosis. Our hypothesis suggests that in the autoimmune process autophagy can intervene at different levels, during the thymic selection process of T lymphocytes causing escape of autoreactive T cells, at the initiation stage of the disease, in the preclinical period or subsequently to the disease onset having a role at the level of perpetuation of the autoimmunity process.Supporting evidence derives from the already reported discovery of polymorphisms in autophagy-related genes in patients affected by several autoimmune conditions such as Systemic Lupus Erithematosus. In addition deregulated autophagy was detected in T cells from lupus-prone mice and also found in T cells from patients. Autophagy was found activated in osteoclasts from RA patients as demonstrated by the increased expression of Atg7 and Beclin-1.Our hypothesis to be unraveled could have, if correct, relevant implications for the management of autoimmune conditions such as Type 1 diabetes. In principle, novel therapeutic approaches could be established by targeting deregulated autophagy offering novel opportunities to personalized medicine in patients affected by the disease. © 2014 Elsevier Ltd. Source


Pham B.N.,Reims University Hospital Center | Musset L.,UF dImmunochimie et Autoimmunite | Chyderiotis G.,Biomnis | Olsson N.O.,CHU Dijon | Fabien N.,Autoimmunity Laboratory
Journal of Digestive Diseases | Year: 2014

Celiac disease is a complex autoimmune disease affecting patients of any age, who may present a wide variety of clinical manifestations. Different guidelines for the diagnosis and management of celiac disease have been recently published. The aim of this study was to determine whether the recommendations issued in these guidelines have been adopted by physicians in France when celiac disease was suspected. Methods: A total of 5521 physicians were asked to fill in a detailed questionnaire on diagnosing celiac disease to evaluate their medical practice, as to the type of symptoms leading to the suspicion of celiac disease, the prescription of duodenal biopsy or serological tests, the type of serological tests (anti-tissue transglutaminase, anti-endomysium, anti-gliadin and anti-reticulin antibodies, total immunoglobulin A measurement) prescribed to diagnose celiac disease. Results: The analysis of the responses of 256 general practitioners (GPs), 221 gastroenterologists and 227 pediatricians showed that the protean clinical presentations of celiac disease might be better recognized by gastroenterologists and pediatricians than by GPs. Gastroenterologists asked for duodenal biopsy much more often than GPs and pediatricians when celiac disease was suspected. Serological testing and knowledge of critical markers, prescribed to diagnose celiac disease, differed among GPs, gastroenterologists and pediatricians. Conclusion: Analysis of medical prescriptions showed that the recommendations for celiac disease diagnosis are not necessarily followed by physicians, emphasizing the fact that the impact of national or international guidelines on medical behavior should be evaluated. © 2014 Chinese Medical Association Shanghai Branch. Source

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