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https://www.readbyqxmd.com/read/29765386/design-of-a-type-1-diabetes-vaccine-candidate-using-edible-plants-expressing-a-major-autoantigen
#1
Edoardo Bertini, Matilde Merlin, Elisa Gecchele, Andrea Puggia, Annalisa Brozzetti, Mauro Commisso, Alberto Falorni, Vittorio Bini, Victor Klymyuk, Mario Pezzotti, Linda Avesani
Type-1 diabetes (T1D) is a metabolic disease involving the autoimmune destruction of insulin-producing pancreatic beta cells. It is often diagnosed by the detection of autoantibodies, typically those recognizing insulin itself or the 65-kDa isoform of glutamic acid decarboxylase (GAD65). Oral insulin can be used to induce systemic immunological tolerance and thus prevent or delay the onset of T1D, suggesting that combination treatments with other autoantigens such as GAD65 could be even more successful. GAD65 has induced oral tolerance and prevented T1D in preclinical studies but it is difficult to produce in sufficient quantities for clinical testing...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29763670/goodpasture-s-autoimmune-disease-a-collagen-iv-disorder
#2
REVIEW
Vadim Pedchenko, A Richard Kitching, Billy G Hudson
Goodpasture's (GP) disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung eliciting rapidly progressive glomerulonephritis and pulmonary hemorrhage. The principal autoantigen is the α345 network of collagen IV, which expression is restricted to target tissues. Recent discoveries include a key role of chloride and bromide for network assembly, a novel posttranslational modification of the antigen, a sulfilimine bond that crosslinks the antigen, and the mechanistic role of HLA in genetic susceptibility and resistance to GP disease...
May 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29760713/human-leukocyte-antigen-class-i-alleles-and-the-autoreactive-t-cell-response-in-psoriasis-pathogenesis
#3
REVIEW
Jörg Christoph Prinz
Psoriasis is a complex immune-mediated inflammatory skin disease characterized by T-cell-driven epidermal hyperplasia. It occurs on a strong genetic predisposition. The human leukocyte antigen (HLA)-class I allele HLA-C*06:02 on psoriasis susceptibility locus 1 (PSORS1 on 6p21.3) is the main psoriasis risk gene. Other HLA-class I alleles encoding HLA molecules presenting overlapping peptide repertoires show associations with psoriasis as well. Outside the major histocompatibility complex region, genome-wide association studies identified more than 60 psoriasis-associated common gene variants exerting only modest individual effects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760702/emerging-concepts-in-immune-thrombocytopenia
#4
REVIEW
Maurice Swinkels, Maaike Rijkers, Jan Voorberg, Gestur Vidarsson, Frank W G Leebeek, A J Gerard Jansen
Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8+ T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8+ Tc targeting megakaryocytes in the bone marrow...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755478/the-contribution-of-autoantibodies-to-inflammatory-cardiovascular-pathology
#5
REVIEW
Lee A Meier, Bryce A Binstadt
Chronic inflammation and resulting tissue damage underlie the vast majority of acquired cardiovascular disease (CVD), a general term encompassing a widely diverse array of conditions. Both innate and adaptive immune mechanisms contribute to chronic inflammation in CVD. Although maladies, such as atherosclerosis and cardiac fibrosis, are commonly conceptualized as disorders of inflammation, the cellular and molecular mechanisms that promote inflammation during the natural history of these diseases in human patients are not fully defined...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755460/proteinase-3-interferes-with-c1q-mediated-clearance-of-apoptotic-cells
#6
Pascale Tacnet-Delorme, Julie Gabillet, Simon Chatfield, Nathalie Thieblemont, Philippe Frachet, Véronique Witko-Sarsat
Proteinase 3 (PR3) is the autoantigen in granulomatosis with polyangiitis, an autoimmune necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Moreover, PR3 is a serine protease whose membrane expression can potentiate inflammatory diseases such as ANCA-associated vasculitis and rheumatoid arthritis. During apoptosis, PR3 is co-externalized with phosphatidylserine (PS) and is known to modulate the clearance of apoptotic cells through a calreticulin (CRT)-dependent mechanism...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29749720/anti-calponin-3-autoantibodies-a-new-specificity-in-patients-with-sj%C3%A3-gren-s-syndrome
#7
Julius Birnbaum, Ahmet Hoke, Aliya Lalji, Peter Calabresi, Pavan Bhargava, Livia Casciola-Rosen
OBJECTIVE: Autoantibodies are clinically useful for phenotyping patients across the spectrum of autoimmune rheumatic diseases. Using serum from a patient with Sjögren's Syndrome (SS), we detected a new specificity by immunoblotting. The purpose of this study was to identify this autoantibody and to evaluate its disease specificity. METHODS: A prominent 40 kDa band was detected when immunoblots were performed using a SS patient serum and lysate from rat dorsal root ganglia (DRG)...
May 11, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29742813/mutated-cancer-autoantigen-implicated-cause-of-paraneoplastic-myasthenia-gravis
#8
Anastasia Zekeridou, Guy E Griesmann, Vanda A Lennon
INTRODUCTION: Anti-tumor immune responses are postulated to initiate paraneoplastic neurological disorders when proteins normally restricted to neural cells are expressed as oncoproteins. Mutated oncopeptides could bypass self-tolerant T-cells to activate cytotoxic effector T-lymphocytes and requisite helper T-lymphocytes to stimulate autoantibody production by B-lymphocytes. METHODS: We investigated muscle-type nicotinic acetylcholine receptor (AChR) antigen expression at transcriptional and protein levels in a small-cell lung cancer line (SCLC) established from a patient with AChR-IgG-positive myasthenia gravis...
May 9, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29734356/microbiota-epitope-similarity-either-dampens-or-enhances-the-immunogenicity-of-disease-associated-antigenic-epitopes
#9
Sebastian Carrasco Pro, Cecilia S Lindestam Arlehamn, Sandeep K Dhanda, Chelsea Carpenter, Mikaela Lindvall, Ali A Faruqi, Clark A Santee, Harald Renz, John Sidney, Bjoern Peters, Alessandro Sette
The microbiome influences adaptive immunity and molecular mimicry influences T cell reactivity. Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes. Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens) were retrieved from the Immune Epitope Database (IEDB). Their similarity to microbiome sequences was calculated using the BLOSUM62 matrix. We found that sequence similarity was associated with either dampened (tolerogenic; e...
2018: PloS One
https://www.readbyqxmd.com/read/29733298/snasp-inhibits-tlr-signaling-to-regulate-immune-response-in-sepsis
#10
Feng-Ming Yang, Yong Zuo, Wei Zhou, Chuan Xia, Bumsuk Hahm, Mark Sullivan, Jinke Cheng, Hui-Ming Chang, Edward Th Yeh
Many Toll-like receptors (TLRs) signal through TNF receptor-associated factor 6 (TRAF6) to activate innate immune responses. Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways...
May 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29720090/sulphite-oxidase-so-a-mitochondrial-autoantigen-as-target-for-humoral-and-cellular-immune-reactions-in-primary-sclerosing-cholangitis
#11
Beate E Preuß, Christoph P Berg, Christoph Werner, Sandra Plankenhorn, Nisar P Malek, Reinhild Klein
BACKGROUND: In a recent study we had evidence that sulphite oxidase (SO) may be a relevant autoantigen in primary sclerosing cholangitis (PSC). Aim of the present study was, therefore, to analyse humoral and cellular immune-reactivity towards SO in these patients in more detail. METHODS: Sera from 53 patients with PSC (30 untreated and 23 treated with ursodeoxycholic acid [UDCA] at time of analysis), from 422 patients with different hepatic and non-hepatic disorders, and from 50 healthy individuals were tested by ELISA for antibodies against full-length-SO (SO-fl) and its three major domains expressed in E...
May 2, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29720035/clinical-application-of-protein-biomarkers-in-lupus-erythematosus-and-lupus-nephritis
#12
S Qi, Q Chen, D Xu, N Xie, Y Dai
Systemic lupus erythematosus (SLE) is a type of autoimmune disease that damages multiple organs, including the heart, joints, liver and kidneys. The main characteristics of SLE are the deposition of circulating autoantibodies; autoantigen complexes in the renal system; and abnormal expression of complements, cytokines and chemokines. Lupus nephritis (LN) is the most serious manifestation of SLE and is characterized by inflammation of the kidney. This review summarizes recent clinical applications of protein biomarkers including autoantibodies, complements, cytokines and chemokines and some new protein biomarkers in SLE and LN...
January 1, 2018: Lupus
https://www.readbyqxmd.com/read/29706966/dysregulated-cd25-and-cytokine-expression-by-%C3%AE-%C3%AE-t-cells-of-systemic-sclerosis-patients-stimulated-with-cardiolipin-and-zoledronate
#13
Helena Migalovich Sheikhet, Jose Villacorta Hidalgo, Paul Fisch, Alexandra Balbir-Gurman, Yolanda Braun-Moscovici, Ilan Bank
Objectives: γδ T cells, a non-conventional innate lymphocyte subset containing cells that can be activated by lipids and phosphoantigens, are abnormally regulated in systemic sclerosis (SSc). To further evaluate the significance of this dysregulation, we compared how exposure to an autoantigenic lipid, cardiolipin (CL), during co-stimulation with an amino-bisphosphonate (zoledronate, zol), affects the activation and cytokine production of SSc and healthy control (HC) γδ T cells. Methods: Expression of CD25 on Vγ9+ , Vδ1+ , and total CD3+ T cells in cultured peripheral blood mononuclear cells (PBMCs), their binding of CD1d tetramers, and the effect of monoclonal antibody (mAb) blockade of CD1d were monitored by flow cytometry after 4 days of in vitro culture...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29706952/b-cell-modulation-strategies-in-autoimmune-diseases-new-concepts
#14
REVIEW
Philippe Musette, Jean David Bouaziz
B cells are major effector cells in autoimmunity through antibody production, T cell help and pro-inflammatory cytokine production. Major advances have been made in human B cell biology knowledge using rituximab and type II new anti-CD20 antibodies, anti-CD19 antibodies, anti-CD22 antibodies, autoantigen specific B cell depleting therapy (chimeric antigen receptor T cells), and B cell receptor signaling inhibition (Bruton's tyrosine kinase inhibitors). However, in certain circumstances B cell depleting therapy may lead to the worsening of the autoimmune disease which is in accordance with the existence of a regulatory B cell population...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29704595/treg-deficiency-leads-to-pathogenic-bp230-autoantibody-and-autoimmune-bullous-disease
#15
Stefanie Haeberle, Xiaoying Wei, Katja Bieber, Stephanie Goletz, Ralf J Ludwig, Enno Schmidt, Alexander H Enk, Eva N Hadaschik
BACKGROUND: Autoimmune bullous dermatoses (AIBD) are severe autoantibody-mediated skin diseases. The pathogenic relevance of autoreactive CD4+ T cells for the induction of autoantibody production remains to be fully evaluated. Scurfy mice lack functional regulatory T cells (Treg), develop spontaneous activation of autoreactive CD4+ T cells and display severe erosive skin lesions suggestive of AIBD. OBJECTIVE: To determine whether AIBD develop in Treg-deficient scurfy mice...
April 25, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29704593/treg-dysfunction-induces-autoantibodies-to-bullous-pemphigoid-antigens-in-mice-and-humans
#16
Ken Muramatsu, Hideyuki Ujiie, Ichiro Kobayashi, Wataru Nishie, Kentaro Izumi, Takamasa Ito, Norihiro Yoshimoto, Ken Natsuga, Hiroaki Iwata, Hiroshi Shimizu
BACKGROUND: Regulatory T cells (Tregs) play a crucial role in peripheral immune tolerance in multiple organs, including the skin. Thus far, the impact of peripheral immune tolerance failure on autoantibody-related autoimmune reaction to the skin is unclear. OBJECTIVE: We sought to elucidate the target autoantigens in the skin under the condition of Treg dysfunction due to Foxp3 gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome...
April 25, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29689721/reaction-of-amyloid-%C3%AE-peptide-antibody-with-different-infectious-agents-involved-in-alzheimer-s-disease
#17
Aristo Vojdani, Elroy Vojdani, Evan Saidara, Datis Kharrazian
As early as the 1980s, molecular virologist Ruth Itzhaki began to investigate if there was a causal connection between infections and neurodegenerative disorder. Although the theory has yet to be universally embraced, in 2016 Itzhaki and 33 other scientists from all over the world published a review article in this very journal presenting evidence for the causal role of pathogens in Alzheimer's disease (AD). Exactly how and in what way pathogens affect the induction of AD has yet to be determined, but one possible answer may involve the cross-reactivity of different pathogens with amyloid-β (Aβ)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29686675/pathogenetic-and-clinical-aspects-of-anti-neutrophil-cytoplasmic-autoantibody-associated-vasculitides
#18
REVIEW
Peter Lamprecht, Anja Kerstein, Sebastian Klapa, Susanne Schinke, Christian M Karsten, Xinhua Yu, Marc Ehlers, Jörg T Epplen, Konstanze Holl-Ulrich, Thorsten Wiech, Kathrin Kalies, Tanja Lange, Martin Laudien, Tamas Laskay, Timo Gemoll, Udo Schumacher, Sebastian Ullrich, Hauke Busch, Saleh Ibrahim, Nicole Fischer, Katrin Hasselbacher, Ralph Pries, Frank Petersen, Gesche Weppner, Rudolf Manz, Jens Y Humrich, Relana Nieberding, Gabriela Riemekasten, Antje Müller
Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29684362/characterization-of-the-small-intestinal-lesion-in-celiac-disease-by-label-free-quantitative-mass-spectrometry
#19
Astrid E V Tutturen, Siri Dørum, Trevor Clancy, Henrik M Reims, Asbjørn Christophersen, Knut E A Lundin, Ludvig M Sollid, Gustavo A de Souza, Jorunn Stamnaes
Global characterization of tissue proteomes from small amounts of biopsy material has become feasible due to advances in mass spectrometry and bioinformatics tools. In celiac disease (CD), dietary gluten induces an immune response which is accompanied by pronounced remodeling of the small intestine. Removal of gluten from the diet abrogates the immune response and the tissue architecture normalizes. In this study differences in global protein expression of small intestinal biopsies from CD patients were quantified by analyzing formalin-fixed, paraffin-embedded material using liquid-chromatography mass spectrometry and label-free protein quantitation...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29674612/autoantibodies-in-myositis
#20
REVIEW
Neil J McHugh, Sarah L Tansley
The discovery of novel autoantigen systems related to idiopathic inflammatory myopathies (collectively referred to as myositis) in adults and children has had major implications for the diagnosis and management of this group of diseases across a wide range of medical specialties. Traditionally, autoantibodies found in patients with myositis are described as being myositis-specific autoantibodies (MSAs) or myositis-associated autoantibodies (MAAs), depending on their prevalence in other, related conditions. However, certain MSAs are more closely associated with extramuscular manifestations, such as skin and lung disease, than with myositis itself...
April 20, 2018: Nature Reviews. Rheumatology
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