 Your new post is loading...
Your new post is loading...
|
Scooped by
Gilbert C FAURE
December 18, 2017 1:44 PM
|
Type 1 diabetes is an autoimmune disease, in which pancreatic β cells are destroyed by autoreactive T cells in genetically predisposed individuals. Serum beta cell autoantibody specificities have represented the mainstay for classifying diabetes as autoimmune-mediated and for stratifying risk in first-degree relatives. In recent years, approaches were attempted to solve the difficult issue of detecting rare antigen-specific autoreactive T cells and their significance to etiopathogenesis such as the use of the MHC multimer technology. This tool allowed the specific detection of increased percentages of GAD65 autoreactive T cells by means of HLA A*02:01 GAD65 AA 114–122 pentamers in newly diagnosed diabetics. Here we provide evidence that GAD65 AA 114–122 pentamers can depict a GAD65 AA114-122 peptide expandable population of functionally and phenotypically skewed, preliminary characterized CD3-CD8dullCD56+ ‘memory-like’ NK cells in PBMC of newly diagnosed diabetics. Our data suggest that the NK cell subset could bind the HLA class I GAD65 AA 114–122 pentamer through ILT2 inhibitory receptor. CD107a expression revealed increased degranulation of CD3-CD8dullCD56+ NK cells in GAD65 AA 114–122 and FLU peptide expanded peripheral blood mononuclear cells of diabetics following GAD65 AA 114–122 peptide HLA A*02:01 presentation in respect to the unpulsed condition. CD107a expression was enriched in ILT2 positive NK cells. As opposite to basal conditions where similar percentages of CD3-CD56+ILT2+ cells were detected in diabetics and controls, CD3-CD56+CD107a+ and CD3-CD56+ILT2+CD107a+ cells were significantly increased in T1D PBMC either GAD65 AA 114–122 or FLU peptides stimulated after co-culture with GAD65 AA 114–122 pulsed APCs. As control, healthy donor NK cells showed similar degranulation against both GAD65 AA 114–122 pulsed and unpulsed APCs. The pathogenetic significance of the CD3-CD8dullCD56+ ‘memory-like NK cell subset’ with increased response upon secondary challenge in diabetics remains to be elucidated.
|
Suggested by
Société Francaise d'Immunologie
December 2, 2017 11:24 AM
|
Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first- or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families.
|
|
Scooped by
Gilbert C FAURE
November 15, 2017 2:32 AM
|
Here we present a collection of key articles from our official journals that investigate type 1 and type 2 diabetes.
|
|
Suggested by
Société Francaise d'Immunologie
November 14, 2017 1:29 PM
|
Few concepts in recent years have garnered more disease research attention than that of the intestinal (i.e. ‘gut’) microbiome. This emerging interest has included investigations of the microbiome'
|
|
Scooped by
Gilbert C FAURE
October 13, 2017 9:40 AM
|
Introduction Recent evidence has demonstrated that, among other factors, dysbiosis (imbalances in the composition and function of the gut microbiota) may be relevant in the development of type 1 diabetes (T1D). Thus, gut microbiota may be a target for improving outcomes in subjects with T1D. The aim of the study is to examine the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed T1D.
Methods and analysis A total of 96 children aged 8 to 17 years with newly diagnosed T1D, confirmed by clinical history and the presence of at least one positive autoantibody, will be enrolled in a double-blind, randomised, placebo-controlled trial in which they will receive L. rhamnosus GG and B. lactis Bb12 at a dose of 109 colony-forming units or an identically appearing placebo, orally, once daily, for 6 months. The follow-up will be for 12 months. The primary outcome measures will be the area under the curve of the C-peptide level during 2-hour responses to a mixed meal.
Ethics and dissemination The Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences.
Trial registration number NCT03032354; Pre-results.
|
|
Scooped by
Gilbert C FAURE
September 14, 2017 9:11 AM
|
National Academy of Sciences
|
|
Scooped by
Gilbert C FAURE
August 28, 2017 9:16 AM
|
A significant leap forward.
|
|
Scooped by
Gilbert C FAURE
August 19, 2017 5:39 AM
|
The natural history of type 1 diabetes (T1D) is challenging to investigate, especially as pre-diabetic individuals are difficult to identify. Numerous T1D consortia have been established to collect whole blood for gene expression analysis from individuals with or at risk to develop T1D. However, with no universally accepted protocol for their collection, differences in sample processing may lead to variances in the results. Here, we examined whether the choice of blood collection tube and RNA extraction kit leads to differences in the expression of genes that are changed during the progression of T1D, and if these differences could be minimized by measuring gene expression directly from the lysate of whole blood. Microarray analysis showed that the expression of 901 genes is highly influenced by sample processing using the PAXgene versus the Tempus system. These included a significant number of lymphocyte-specific genes and genes whose expression has been reported to differ in the peripheral blood of at-risk and T1D patients compared to controls. We showed that artificial changes in gene expression occur when control and T1D samples were processed differently. The sample processing-dependent differences in gene expression were largely due to loss of transcripts during the RNA extraction step using the PAXgene system. The majority of differences were not observed when gene expression was measured in whole blood lysates prepared from blood collected in PAXgene and Tempus tubes. We showed that the gene expression profile of samples processed using the Tempus system is more accurate than that of samples processed using the PAXgene system. Variation in sample processing can result in misleading changes in gene expression. However, these differences can be minimized by measuring gene expression directly in whole blood lysates.
|
|
Suggested by
Société Francaise d'Immunologie
August 19, 2017 5:33 AM
|
Immunology and Cell Biology focuses on the general functioning of the immune system in its broadest sense, with a particular emphasis on its cell biology. Areas that are covered include but are not limited to: Cellular immunology, Innate and adaptive immunity, Immune responses to pathogens,Tumour immunology,Immunopathology, Immunotherapy, Immunogenetics, Immunological studies in humans and model organisms (including mouse, rat, Drosophila etc)
|
|
Scooped by
Gilbert C FAURE
August 8, 2017 8:48 AM
|
Type 1 diabetes (T1D) is a chronic autoimmune disease that causes severe loss of pancreatic β cells. Autoreactive T cells are key mediators of β cell destruction. Studies of organ donors with T1D that have examined T cells in pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a broad repertoire of target antigens and T cell receptor (TCR) usage, with initial evidence of public TCR sequences that are shared by individuals with T1D. Neoepitopes derived from post-translational modifications of native antigens are emerging as novel targets that are more likely to evade self-tolerance. Further studies will determine whether T cell responses to neoepitopes are major disease drivers that could impact prediction, prevention, and therapy. This Review provides an overview of recent progress in our knowledge of autoreactive T cells that has emerged from experimental and clinical research as well as pathology investigations.
|
|
Scooped by
Gilbert C FAURE
July 18, 2017 2:09 PM
|
National Academy of Sciences
|
Suggested by
LIGHTING
July 7, 2017 1:55 PM
|
CD38 is an activation marker that is present on recently activated T cells, but absent on resting memory T cells. In this study, we show that CD45RO+CD38+ β cell Ag-specific CD4+ T cells were present at higher frequencies in type 1 diabetes subjects compared with those in healthy subjects. These results imply an ongoing β cell immunity years after onset of diabetes and suggest these activated T cells have an active role in the disease process. The Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope mapping assay. Although each patient usually had a unique set of epitopes recognized by these T cells, two epitopes, DR0401-restricted modified preproinsulin peptide 78–90K88S and zinc transport 8 266–285, were repeatedly identified in multiple subjects. Identifying these T cells and their specific antigenic epitopes might provide immunotherapeutic targets for personalized therapies.
|
|
Scooped by
Gilbert C FAURE
July 1, 2017 5:03 AM
|
Coeliac disease (CD) is a common condition with significant implications for health and future development that benefits from early identification and treatment. The interaction with other autoimmune conditions, such as type 1 diabetes mellitus (T1DM), and overlap with other more functional conditions, such as wheat sensitivity, has led clinicians to consider strategies to risk-stratify the likelihood of CD.
The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidance1 states that CD diagnosis can be made without biopsy in patients symptomatic on a gluten-containing diet, with 1) tissue transglutaminase antibody (tTG) IgA >10× upper limit of normal, 2) positive antiendomysial antibodies and 3) HLA-DQ2 or HLA-DQ8 positivity. This strategy is to reduce the numbers (and cost) needing endoscopy and shorten the time to initiating treatment. The two additional indications for human leucocyte antigen (HLA) testing are at the time of diagnosis of an autoimmune condition and those with gut or other symptoms, whose parents initiate a wheat or gluten-free diet (GFD), with symptomatic improvement. For those with other autoimmune conditions with HLA-DQ2 or HLA-DQ8 positivity, ESPGHAN suggest tTG IgA 3 yearly based on expert opinion; for those HLA-DQ2 or HLA-DQ8 negative …
|
|
|
Scooped by
Gilbert C FAURE
December 18, 2017 11:10 AM
|
Type 1 diabetes (T1D) has a strong genetic component. The insulin dependent diabetes ( Idd ) 22 locus was identified in crosses of T1D-susceptible NOD mice with the strongly T1D-resistant ALR strain. The NODcALR-( D8Mit293-D8Mit137 )/Mx (NOD- Idd22 ) recombinant congenic mouse strain was generated in which NOD mice carry the full Idd22 confidence interval. NOD- Idd22 mice exhibit almost complete protection from spontaneous T1D and a significant reduction in insulitis. Our goal was to unravel the mode of Idd22 -based protection using in vivo and in vitro models. We determined that Idd22 did not impact immune cell diabetogenicity or β cell resistance to cytotoxicity in vitro. However, NOD- Idd22 mice were highly protected against adoptive transfer of T1D. Transferred CTLs trafficked to the pancreatic lymph node and proliferated to the same extent in NOD and NOD- Idd22 mice, yet the accumulation of pathogenic CTLs in the islets was significantly reduced in NOD- Idd22 mice, correlating with disease resistance. Pancreatic endothelial cells from NOD- Idd22 animals expressed lower levels of adhesion molecules, even in response to inflammatory stimuli. Lower adhesion molecule expression resulted in weaker adherence of T cells to NOD- Idd22 endothelium compared with NOD-derived endothelium. Taken together, these results provide evidence that Idd22 regulates the ability of β cell–autoreactive T cells to traffic into the pancreatic islets and may represent a new target for pharmaceutical intervention to potentially prevent T1D.
|
|
Scooped by
Gilbert C FAURE
November 17, 2017 7:24 AM
|
In type 1 diabetes, autoreactive CD4 T cells attack and kill pancreatic β cells, disrupting insulin production. Many approaches have been taken to inhibit this process, but few have translated into real benefit for diabetic patients. Ben Nasr et al. demonstrate that hematopoietic stem and progenitor cells from NOD mice and diabetic patients express less PD-L1, which is a T cell inhibitory molecule. Induction of PD-L1 expression on stem cells reversed diabetes in NOD mice and inhibited human autoimmune responses in vitro. Either gene therapy or pharmacological modulation of PD-L1 on stem cells could be brought into the clinic, providing a new way to interrupt the autoimmune response and help people with diabetes.
|
|
Scooped by
Gilbert C FAURE
November 14, 2017 1:33 PM
|
National Academy of Sciences
|
|
Scooped by
Gilbert C FAURE
November 7, 2017 11:36 AM
|
Type 1 diabetes (T1D) is one of the most common and severe chronic diseases affecting both children and adults. The aetiology of the disease remains unknown, and thus far no ‘true’ cure for thos
|
|
Scooped by
Gilbert C FAURE
October 10, 2017 8:29 AM
|
Scientists have discovered that the onset of type 1 diabetes is preceded by modification of MAIT lymphocytes. These cells—associated with mucosae and able to recognize elements of the microbiota—could therefore serve as new biomarkers for early detection and prevention of the illness.
|
|
Scooped by
Gilbert C FAURE
September 14, 2017 9:10 AM
|
Researchers from the Johns Hopkins University School of Medicine, Stanford University and the University of Florida report the development of a novel antibody detection technology that holds promise for improving the accurac
|
|
Scooped by
Gilbert C FAURE
August 24, 2017 4:13 AM
|
Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet
|
|
Scooped by
Gilbert C FAURE
August 19, 2017 5:38 AM
|
PR Newswire
NEW YORK, Aug. 18, 2017
NEW YORK, Aug. 18, 2017 /PRNewswire/ -- IBM (NYSE: IBM) and JDRF, the leading global organization funding type 1 diabetes (T1D) research, today announced a new collabor
|
|
Scooped by
Gilbert C FAURE
August 13, 2017 1:21 PM
|
Immunotherapy using peptides has been successful for some patients with allergies, but has not yet been deployed in autoimmune diseases, which may involve greater safety risks. Alhadj Ali et al . designed a placebo-controlled trial to determine whether a proinsulin peptide could safely elicit immune and metabolic responses in people recently diagnosed with type 1 diabetes without accelerating disease. This small trial showed that treatment seemed to modify T cell responses and did not interfere with residual β cell function. In contrast to subjects in the placebo arm, treated subjects did not need to increase their insulin use. These encouraging results support a larger trial to investigate efficacy of the peptide therapy for treating disease.
|
|
Suggested by
LIGHTING
July 29, 2017 2:02 PM
|
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined. In this study, NOD mice deficient for the HR have been generated by means of IL-13Rα1 gene disruption and used to determine whether such deficiency affects the development of T1D. Surprisingly, the findings indicate that NOD mice lacking the HR (13R−/−) display resistance to T1D as the rise in blood glucose level and islet inflammation were significantly delayed in these HR-deficient relative to HR-sufficient (13R+/+) mice. In fact, the frequency and spleen-to-pancreas dynamics of both Th1 and Th17 cells were affected in 13R−/− mice. This is likely due to an increase in the frequency of mTGFβ+Foxp3int regulatory T cells and the persistence of CD206+ macrophages in the pancreas as both types of cells confer resistance to T1D upon transfer to 13R+/+ mice. These findings reveal new insights as to the role environmental IL-4/IL-13 and the HR play in peripheral tolerance and the development of T1D.
|
|
Scooped by
Gilbert C FAURE
July 18, 2017 7:09 AM
|
Although many approaches have been tested to overcome the insulin dependence caused by the pancreatic β-cells destruction observed in individuals affected by type 1 diabetes (T1D), medical research ha
Recent evidences suggest that human gut microbiota with major component as bacteria can induce immunity. It is also known that gut lining depletes with ageing and that there is increased risk of autoimmune and inflammatory disorders with ageing. It is therefore likely that both may be correlated as depletion of gut lining exposes the gut bacterial antigens to host immune mechanisms, which may induce immunity to certain bacterial proteins, but at the same time such immunity may also be auto-immunogenic to host. This autoimmunity may make a protein molecule nonfunctional and thereby may be involved in late onset metabolic, autoimmune and inflammatory disorders such as, Diabetes, Rheumatoid Arthritis, Hyperlipidemias and Cancer. In this in-silico study we found a large number of peptides identical between human and gut bacteria which were binding to HLA-II alleles, and hence, likely to be auto-immunogenic. Further we observed that such autoimmune candidates were enriched in bacterial species belonging to Firmicutes and Proteobacteria phyla, which lead us to conclude that these phyla may have higher disease impact in genetically predisposed individuals. Functional annotation of human proteins homologous to candidate gut-bacterial peptides showed significant enrichment in metabolic processes and pathways. Cognitive trait, Ageing, Alzheimer, Type 2 diabetes, Chronic Kidney Failure (CKF), Chronic Obstructive Pulmonary Disease (COPD) and various Cancers were the major diseases represented in the dataset. This dataset provides us with gut bacterial autoimmune candidates which can be studied for their clinical significance in late onset diseases.
Via Krishan Maggon
|
![Immunology and Cell Biology - Dominant TNF[alpha] and impaired IL-2 cytokine profiles of CD4+ T cells from children with type-1 diabetes | AUTOIMMUNITY | Scoop.it](https://img.scoop.it/3_1hz4UZGz55qIjx0SO_6Dl72eJkfbmt4t8yenImKBVvK0kTmF0xjctABnaLJIm9)
