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https://www.readbyqxmd.com/read/28625726/pulmonary-administration-of-soluble-antigen-arrays-is-superior-to-antigen-in-treatment-of-experimental-autoimmune-encephalomyelitis
#1
Christopher Kuehl, Sharadvi Thati, Bradley Sullivan, Joshua Sestak, Michael Thompson, Teruna Siahaan, Cory Berkland
Antigen-specific immunotherapy (ASIT) has been used to hyposensitize patients to allergens and offers an enticing approach for attenuating autoimmune diseases. Applying ASIT to mucosal surfaces such as the lungs may engage unique immune response pathways to improve efficacy. Pulmonary delivery of soluble antigen arrays (SAgAs) was explored in mice with experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. SAgAs were designed to impede immune response to autoantigen epitopes and are composed of a hyaluronan backbone with peptides PLP139-151 and LABL, a disease-causing proteolipid peptide epitope and an ICAM-1 ligand, respectively...
June 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#2
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28600290/high-throughput-single-cell-analysis-of-b-cell-receptor-usage-among-autoantigen-specific-plasma-cells-in-celiac-disease
#3
Bishnudeo Roy, Ralf S Neumann, Omri Snir, Rasmus Iversen, Geir Kjetil Sandve, Knut E A Lundin, Ludvig M Sollid
Characterization of Ag-specific BCR repertoires is essential for understanding disease mechanisms involving humoral immunity. This is optimally done by interrogation of paired H chain V region (VH) and L chain V region (VL) sequences of individual and Ag-specific B cells. By applying single-cell high-throughput sequencing on gut lesion plasma cells (PCs), we have analyzed the transglutaminase 2 (TG2)-specific VH:VL autoantibody repertoire of celiac disease (CD) patients. Autoantibodies against TG2 are a hallmark of CD, and anti-TG2 IgA-producing gut PCs accumulate in patients upon gluten ingestion...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28597552/branched-chain-%C3%AE-ketoacid-dehydrogenase-kinase-111-130-a-t-cell-epitope-that-induces-both-autoimmune-myocarditis-and-hepatitis-in-a-j-mice
#4
Bharathi Krishnan, Chandirasegaran Massilamany, Rakesh H Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A Uzal, Jennifer L Strande, Gustavo A Delhon, Jean-Jack Riethoven, David Steffen, Jay Reddy
INTRODUCTION: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread. METHODS: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKDk ) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver...
June 9, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28593827/liposome-based-immunotherapy-against-autoimmune-diseases-therapeutic-effect-on-multiple-sclerosis
#5
Irma Pujol-Autonell, Maria-Jose Mansilla, Silvia Rodriguez-Fernandez, Mary Cano-Sarabia, Juan Navarro-Barriuso, Rosa-Maria Ampudia, Aleix Rius, Sonia Garcia-Jimeno, David Perna-Barrull, Eva Martinez-Caceres, Daniel Maspoch, Marta Vives-Pi
AIM: Based on the ability of apoptosis to induce immunological tolerance, liposomes were generated mimicking apoptotic cells, and they arrest autoimmunity in Type 1 diabetes. Our aim was to validate the immunotherapy in other autoimmune disease: multiple sclerosis. MATERIALS & METHODS: Phosphatidylserine-rich liposomes were loaded with disease-specific autoantigen. Therapeutic capability of liposomes was assessed in vitro and in vivo. RESULTS: Liposomes induced a tolerogenic phenotype in dendritic cells, and arrested autoimmunity, thus decreasing the incidence, delaying the onset and reducing the severity of experimental disease, correlating with an increase in a probably regulatory CD25(+) FoxP3(-) CD4(+) T-cell subset...
June 2017: Nanomedicine
https://www.readbyqxmd.com/read/28590036/t-regulatory-cells-and-other-lymphocyte-subsets-in-patients-with-bullous-pemphigoid
#6
T Gambichler, A Tsitlakidon, M Skrygan, S Höxtermann, L Susok, S Hessam
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease, and is associated with autoantibodies to the hemidesmosomal BP autoantigens BPAG1 and BPAG2. AIM: We aimed to investigate the significance of T regulatory cells and other lymphocyte subsets in patients with BP. METHODS: In total, 31 inpatients with BP were treated with systemic prednisolone in a tapered dose regimen, while 28 healthy individuals matched for age and sex served as the healthy control (HC) group...
June 7, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28584006/activated-b-cells-participating-in-the-anti-myelin-response-are-excluded-from-the-inflamed-central-nervous-system-in-a-model-of-autoimmunity-that-allows-for-b-cell-recognition-of-autoantigen
#7
Yodit Tesfagiorgis, Sarah L Zhu, Rajiv Jain, Steven M Kerfoot
Once activated, T cells gain the ability to access both healthy and inflamed nonlymphoid tissues. They are then reactivated to remain in the tissue and exert their effector function only if they encounter their specific Ag. In this study, we set out to determine if the same is true for B cells using a mouse model of CNS autoimmunity that incorporates both T and B cell recognition of a myelin autoantigen. Both T and B cells were common infiltrates of spinal cords in diseased mice. However, unlike T cells, anti-myelin B cells were excluded from the inflamed tissue...
June 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28581446/tregs-restrain-dendritic-cell-autophagy-to-ameliorate-autoimmunity
#8
Themis Alissafi, Aggelos Banos, Louis Boon, Tim Sparwasser, Alessandra Ghigo, Kajsa Wing, Dimitrios Vassilopoulos, Dimitrios Boumpas, Triantafyllos Chavakis, Ken Cadwell, Panayotis Verginis
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28581157/novel-furan-containing-peptide-based-inhibitors-of-protein-arginine-deiminase-type-iv-pad4
#9
Chian Ying Teo, Bimo A Tejo, Adam Thean Chor Leow, Abu Bakar Salleh, Mohd Basyaruddin Abdul Rahman
Protein arginine deiminase type IV (PAD4) is responsible for the post-translational conversion of peptidylarginine to peptidylcitrulline. Citrullinated protein is the autoantigen in rheumatoid arthritis, and therefore, PAD4 is currently a promising therapeutic target for the disease. Recently, we reported the importance of the furan ring in the structure of PAD4 inhibitors. In this study, the furan ring was incorporated into peptides to act as the "warhead" of the inhibitors for PAD4. IC50 studies showed that the furan-containing peptide-based inhibitors were able to inhibit PAD4 to a better extent than the furan-containing small molecules that were previously reported...
June 5, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28579863/is-tolerance-broken-in-autoimmunity
#10
EDITORIAL
Dama Laxminarayana
Autoimmune diseases are classified into about 80 different types based on their specificity related to system, organ and/or tissue. About 5% of the western population is affected by this anomaly, but its worldwide incidence is unknown. Autoimmune diseases are heterogeneous in nature and clinical manifestations range from benign disorders to life-threatening conditions. Autoimmunity strikes at any stage of life, but age and/or gender also play role in onset of some of these anomalies. The autoimmune pathogenesis is initiated by the origination of autoantigens, which leads to the development of autoantibodies followed by auto-immunogenicity and the ultimate onset of autoimmunity...
2017: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/28578649/peptides-against-autoimmune-neurodegeneration
#11
Alexey Stepanov, Yakov Lomakin, Alexander Gabibov, Alexey Belogurov
The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body...
June 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28577873/increased-circulating-autoantibodies-levels-of-igg-iga-igm-against-cytokeratin-18-and-cytokeratin-19-in-chronic-obstructive-pulmonary-disease
#12
Yin Xiong, Sihai Gao, Guangwei Luo, Guilian Cheng, Wei Huang, Rui Jiang, Yueqin Wang, Tianpen Cui
BACKGROUND AND AIMS: Autoimmune processes are involved in the progression of chronic obstructive pulmonary disease (COPD). Autoantibodies against cytokeratin 18 (CK18) and cytokeratin 19 (CK19) could be associated with lung injury. We undertook this study to investigate the role of these autoantibodies against CK18 and CK19 in the development of COPD. METHODS AND RESULTS: We used blood samples from 228 COPD patients or 136 healthy controls and male C57BL/6j mice as experimental subjects to analyze the serum autoantibody levels against CK18 or CK19 autoantigen by enzyme-linked immunosorbent assay (ELISA)...
January 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28577748/-membranous-nephropathy-new-insights-in-therapeutic-approach
#13
Karine Dahan
Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults, evolving to 30 % end-stage renal disease after 10 years, in the absence of specific treatment. In 2009, the M-type phospholipase A2 receptor (PLA2R), a podocyte membrane glycoprotein, was identified as the first autoantigen involved in more than 70 % of primitive membranous nephropathy. Many studies have reported that high titers of PLA2R antibodies are correlated with a lower risk of spontaneous or immunosuppressant-induced remission, a higher risk of nephrotic syndrome and of progression to end-stage renal disease...
April 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28570922/the-critical-amino-acids-of-a-nephritogenic-epitope-on-human-goodpasture-autoantigen-for-binding-to-hla-drb1-1501
#14
Qiu-Hua Gu, Xiao-Yu Jia, Jian-Nan Li, Fang-Jin Chen, Zhao Cui, Ming-Hui Zhao
BACKGROUND: Anti-GBM disease is caused by autoimmunity to Goodpasture antigen on α3(IV)NC1 and had strong associations with HLA-DRB1*1501. Previous studies identified α3127-148 (P14: TDIPPCPHGWISLWKGFSFIMF) as a T cell epitope. The present study was aimed to investigate the binding capacity of P14 to HLA-DRB1*1501 and the critical amino acids for this binding. METHODS: A line of EBV-transformed human B cells homozygous for HLA-DRB1*1501 was used to detect the binding capacity of peptides to HLA-DRB1*1501 using flow cytometry analysis...
May 29, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28566539/role-of-the-immune-system-in-hypertension
#15
REVIEW
Bernardo Rodriguez-Iturbe, Hector Pons, Richard J Johnson
High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28561044/engineered-clearing-agents-for-the-selective-depletion-of-antigen-specific-antibodies
#16
Siva Charan Devanaboyina, Priyanka Khare, Dilip K Challa, Raimund J Ober, E Sally Ward
Here we have designed a novel class of engineered antibody-based reagents ('Seldegs') that induce the selective degradation of antigen-specific antibodies. We demonstrate the rapid and specific clearance of antibodies recognizing the autoantigen, myelin oligodendrocyte glycoprotein and tumour target, HER2. Seldegs have considerable potential in multiple areas, including the treatment of antibody-mediated autoimmunity and diagnostic imaging.
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28557628/identification-of-endothelin-converting-enzyme-2-as-an-autoantigen-in-autoimmune-polyendocrine-syndrome-type-1
#17
Casey J A Smith-Anttila, Sophie Bensing, Mohammad Alimohammadi, Frida Dalin, Mikael Oscarson, Ming-Dong Zhang, Jaakko Perheentupa, Eystein S Husebye, Jan Gustafsson, Peyman Björklund, Anette Fransson, Gunnel Nordmark, Lars Rönnblom, Antonella Meloni, Rodney J Scott, Tomas Hökfelt, Patricia A Crock, Olle Kämpe
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen...
May 30, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28554330/rho-associated-protein-kinase-2-rock2-a-new-target-of-autoimmunity-in-paraneoplastic-encephalitis
#18
Stoyan Popkirov, Ilya Ayzenberg, Stefanie Hahn, Jan Bauer, Yvonne Denno, Nicole Rieckhoff, Christiane Radzimski, Volkmar H Hans, Sebastian Berg, Florian Roghmann, Joachim Noldus, Christian G Bien, Sabine Skodda, Jörg Wellmer, Winfried Stöcker, Christos Krogias, Ralf Gold, Uwe Schlegel, Christian Probst, Lars Komorowski, Ramona Miske, Ingo Kleiter
Onconeural antibodies are associated with cancer and paraneoplastic encephalitis. While their pathogenic role is still largely unknown, their high diagnostic value is undisputed. In this study we describe the discovery of a novel target of autoimmunity in an index case of paraneoplastic encephalitis associated with urogenital cancer.A 75-year-old man with a history of invasive bladder carcinoma 6 years ago with multiple recurrences and a newly discovered renal cell carcinoma presented with seizures and progressive cognitive decline followed by super-refractory status epilepticus...
May 29, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28550388/antibodies-against-linear-epitopes-on-goodpasture-autoantigen-in-patients-with-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis
#19
Xiao-Yu Jia, Jun-Tao Yu, Shui-Yi Hu, Jian-Nan Li, Miao Wang, Chen Wang, Min Chen, Zhao Cui, Ming-Hui Zhao
In a substantial number of patients with crescentic glomerulonephritis, both anti-glomerular basement membrane (GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA) are detected simultaneously. ANCA is presumed to be the initial event but the mechanism is unknown. In the present study, we investigated the antibodies against linear epitopes on Goodpasture autoantigen in sera from patients with ANCA-associated vasculitis, aiming to reveal the mechanisms of the coexistence of the two kinds of autoantibodies...
May 26, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28546501/proteinase-3-the-odd-one-out-that-became-an-autoantigen
#20
REVIEW
Katherine R Martin, Véronique Witko-Sarsat
Neutrophils are critical in the defense against bacterial and fungal pathogens, and they also modulate the inflammatory process. The areas where neutrophils are studied have expanded from the restricted field of antibacterial defense to the modulation of inflammation and finally, to fine-tuning immune responses. As a result, recent studies have shown that neutrophils are implicated in several systemic autoimmune diseases, although exactly how neutrophils contribute to these diseases and the molecular mechanisms responsible are still under investigation...
May 25, 2017: Journal of Leukocyte Biology
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