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Scooped by
Gilbert C FAURE
March 2, 2018 4:08 AM
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We stratified patients into five subgroups with differing disease progression and
risk of diabetic complications. This new substratification might eventually help to
tailor and target early treatment to patients who would benefit most, thereby representing
a first step towards precision medicine in diabetes.
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Suggested by
Société Francaise d'Immunologie
February 27, 2018 1:12 PM
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Scooped by
Gilbert C FAURE
February 27, 2018 2:13 AM
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To the Editor:
Innate immune receptors have been found to be involved in the pathogenesis of systemic lupus erythematosus (SLE)1. The binding of nucleic acids to the endosomal Toll-like receptors (TLR) 7 and TLR9 is considered as a triggering mechanism for the production of antinuclear antibodies2,3. Also, the cell membrane-bound TLR (mbTLR) might contribute to enhance immune cell responses in SLE. Besides detecting microorganisms, these receptors engage molecules exposed upon apoptosis, such as the DNA-binding high mobility group protein B1, which is thought to facilitate self-DNA antigenicity4. The contribution of the mbTLR TLR2 and TLR4 to loss of tolerance and development of nephritis has been consistently found in SLE models conducted in transgenic mice5,6,7. However, there is little information about the activation of mbTLR during SLE flares in humans.
We have studied TLR2 and TLR4 protein levels in peripheral blood mononuclear cells from patients with SLE (n = 35) and healthy controls (n = 11) using flow cytometry. Patients were receiving stable medication at the time of the study, and had no signs of active infection. Whereas no global differences in the levels of the mbTLR were noted between the cohorts, the density of TLR4 was significantly increased in the B cells of patients with active (n = 20) …
Address correspondence to Dr. O. Sánchez-Pernaute, Division of Rheumatology, Jiménez Díaz Foundation Health Research Institute and University Hospital, Avda. Reyes Católicos 2, 28040 Madrid, Spain. E-mail: osanchez{at}fjd.es
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
February 24, 2018 11:05 AM
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Suggested by
Société Francaise d'Immunologie
February 17, 2018 3:19 AM
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Background: B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC). Methods: Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gender-matched HC. We determined the frequencies of different B-cell subsets in peripheral blood naïve and memory compartments. In addition, we measured serum B cell-activating factor (BAFF) levels and circulating pro-inflammatory cytokines, such as IL-6, by commercial ELISA and CBA, respectively. Results: Patients with pAPS showed a lower percentage of immature and naïve B cells than patients with SLE (p = 0.013 and p = 0.010, respectively) and a higher percentage of non-switched memory B cells than patients with SLE (p = 0.001). No differences either in the percentage of switched memory cells or plasma cells were found among the different groups. Serum BAFF levels were higher in SLE patients than in healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). A significant increase in the serum BAFF levels was also observed in pAPS patients compared to HC (p = 0.047). Circulating IL-6 levels were higher in SLE and pAPS patients than HC (p = 0.036 and p = 0.048, respectively). A positive correlation was found between serum BAFF and IL-6 levels in patients with SLE but not in pAPS (p = 0.011). Conclusions: Our characterization of peripheral blood B-cell phenotypes in pAPS demonstrates different frequencies of circulating B cells at different stages of differentiation. These differences in the naïve B-cell repertoire could explain the higher number and variety of autoantibodies in SLE patients in comparison to pAPS patients, especially in those with obstetric complications.
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Scooped by
Gilbert C FAURE
February 16, 2018 10:57 AM
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A drug commonly used to control high blood pressure may also help prevent the onset of type 1 diabetes in up to 60 percent of those at risk for the disease, according to researchers at the University of Colorado Anschutz Medical Campus and the University of Florida in Gainesville.
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Scooped by
Gilbert C FAURE
February 16, 2018 10:55 AM
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Anti-Saccharomyces cerevisiae Autoantibodies in AutoimmuneDiseases: from Bread Baking to Autoimmunity
Maurizio Rinaldi &
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Scooped by
Gilbert C FAURE
February 15, 2018 8:13 AM
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Although natural killer (NK) cells have been implicated in the pathogenesis of type 1 diabetes, the mechanism whereby they contribute to this autoimmune disorder—which depends on destruction of pancreatic beta cells by autoreactive T cells—has been unclear. Gur et al . wondered whether natural cytotoxicity receptor NKp46, an activating NK cell receptor that has been implicated in tumor immunity and control of influenza despite having no known ligand (see Colucci and Cilio), might play a role. They found that fusion proteins of NKp46 or the mouse ortholog NCR1 with immunoglobulin (NKp46-Ig and NCR1-Ig, respectively) recognized human and mouse beta cells but no other pancreatic cells. Immunohistochemical analysis of nonobese diabetic mice (NOD mice, a model of type 1 diabetes) revealed that the NKp46 ligand was present before the development of the pancreatic islet inflammation that precedes diabetes (insulinitis) and throughout the development of diabetes. A comparison of mouse NK cells with NCR1 to NK cells lacking NCR1 indicated that, although beta cells failed to elicit cytokine secretion, they stimulated NK cell degranulation; indeed, NK cells isolated from islets of prediabetic NOD mice showed substantial degranulation. Mice lacking NCR1 were resistant to the development of type 1 diabetes in response to injection with low-dose streptozotocin (LDST), and NK cells appeared in the pancreas of NOD and LDST mice during insulinitis, becoming most abundant at the prediabetic stage, during the transition from insulinitis to diabetes. Injection of NKp46-Ig or NCR1-Ig into NOD mice, which stimulated the production of antibodies directed against NKp46 or NCR1, respectively, decreased the surface abundance of NCR1, inhibited beta cell–induced NK cell degranulation, and prevented the development of diabetes, even when administered at the late prediabetic stage. The authors thus conclude that a ligand to NKp46 is present on pancreatic beta cells and that this NK cell receptor is crucial to the development of type 1 diabetes.
C. Gur, A. Porgador, M. Elboim, R. Gazit, S. Mizrahi, N. Stern-Ginossar, H. Achdout, H. Ghadially, Y. Dor, T. Nir, V. Doviner, O. Hershkovitz, M. Mendelson, Y. Naparstek, O. Mandelboim, The activating receptor NKp46 is essential for the development of type 1 diabetes. Nat. Immunol. 11 , 121–128 (2010). [[PubMed]][1]
F. Colucci, C. M. Cilio, Taming killer cells may halt diabetes progression. Nat. Immunol. 11 , 111–112 (2010). [[PubMed]][2]
[1]: http://www.ncbi.nlm.nih.gov/pubmed/20023661
[2]: http://www.ncbi.nlm.nih.gov/pubmed/20084067
Background/purpose One to three per cent of the world’s population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated wit
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
February 12, 2018 8:36 AM
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Cell Mol Immunol. 2018 Feb 5. doi: 10.1038/cmi.2017.140. [Epub ahead of print]
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Scooped by
Gilbert C FAURE
February 12, 2018 8:33 AM
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Curr Mol Med. 2018 Feb 7. doi: 10.2174/1566524018666180207155614. [Epub ahead of print]
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Scooped by
Gilbert C FAURE
February 12, 2018 5:09 AM
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A spit test is being developed that could be used to make diagnosing type 1 diabetes easier in children. Leading type 1 diabetes charity JDRF has partnered with Enable Biosciences to develop a spit-to-screen scheme which could remove obstacles in diagnosing children with the autoimmune disease.
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Scooped by
Gilbert C FAURE
March 1, 2018 5:53 AM
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Suggested by
Société Francaise d'Immunologie
February 27, 2018 1:12 PM
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Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the loss of adaptive immune tolerance to nucleic acid containing antigens. The resulting autoantibodies form immune complexes that promote inflammation and tissue damage. Defining the signals that drive pathogenic autoantibody production is an important step in the development of more targeted therapeutic approaches for lupus, which is currently treated primarily with non-specific immunosuppression. Here, we review the contribution of Bruton’s tyrosine kinase (Btk), a component of B and myeloid cell signaling pathways, to disease in murine lupus models. Both gain- and loss-of-function genetic studies have revealed that Btk plays multiple roles in the production of autoantibodies. These include promoting the activation, plasma cell differentiation, and class switching of autoreactive B cells. Small molecule inhibitors of Btk are effective at reducing autoantibody levels, B cell activation, and kidney damage in several lupus models. These studies suggest that Btk may promote end organ damage both by facilitating the production of autoantibodies and by mediating the inflammatory response of myeloid cells to these immune complexes. While Btk has not been associated with SLE in GWAS studies, SLE B cells display signaling defects in components both upstream and downstream of Btk consistent with enhanced activation of Btk signaling pathways. Taken together, these observations indicate that limiting Btk activity is critical for maintaining B cell tolerance and preventing the development of autoimmune disease. Btk inhibitors, generally well-tolerated and approved to treat B cell malignancy, may thus be a useful therapeutic approach for SLE.
Type I interferons (IFNs) have a prominent role in many aspects of normal innate and adaptive immunity and autoimmunity. However, cell-type specific information about type I IFN expression and autocrine/paracrine signaling is sparse and mostly focused on non-lymphocyte and non-immune .
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
February 25, 2018 1:40 PM
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Mitochondria are essential to keep cells alive, but when damaged, they can trigger the body’s own immune system with potentially devastating consequences.
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Scooped by
Gilbert C FAURE
February 18, 2018 1:26 PM
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Alvan Feinstein, both a clinician and an epidemiologist, introduced the concept of comorbidity as a peculiar and important feature of chronic diseases almost 50
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Scooped by
Gilbert C FAURE
February 16, 2018 10:57 AM
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Abstract. Objective. Exposure to illicit cocaine and its frequent adulterant, levamisole, is associated with ANCAs targeting neutrophil elastase (NE), neutrope
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Scooped by
Gilbert C FAURE
February 16, 2018 10:56 AM
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ImmunoQure will collaborate with Servier to advance ImmunoQure's therapeutic human Interferon-α autoantibody through preclinical development and into the clinic where Servier will be entrusted with the responsibility for its development as therapeutic to treat diseases driven by human Interferon-α autoantibody
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Scooped by
Gilbert C FAURE
February 16, 2018 10:54 AM
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Autoimmunity is accepted as the origin or amplifier of various diseases. In the mid-1970s, a new class of “so-called” functional autoantibodies that bind to G-protein-coupled receptors (GPCR-AABs) was identified for downstream pathologies.
Review
An important role also exists for the target tissue (exocrine glands, namely the salivary and lachrymal glands), which promotes local B cell activation. This continuous stimulation of B cells is the main driver of lymphomatous escape. Identification of the multiple steps that support B cell activation has led to the development of promising targeted therapies that will hopefully lead to the development of an efficient therapeutic strategy for pSS.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
February 12, 2018 8:37 AM
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J Med Internet Res. 2018 Jan 18;20(1):e14. doi: 10.2196/jmir.7683.
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Scooped by
Gilbert C FAURE
February 12, 2018 8:33 AM
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Ther Adv Neurol Disord. 2017 Aug 16;11:1756285617722347. doi: 10.1177/1756285617722347. eCollection 2018. Review
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Scooped by
Gilbert C FAURE
February 12, 2018 5:11 AM
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TheTribune: CHANDIGARH:Hundreds of patients visiting the Postgraduate Institute of Medical Education and Research (PGIMER) are at the receiving end as the tests for autoimmune diseases are not being conducted at the institute since January 25.
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