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https://www.readbyqxmd.com/read/29776017/pharmacokinetics-and-c-reactive-protein-modelling-of-anti-il-6-antibody-pf-04236921-in-healthy-volunteers-and-patients-with-autoimmune-disease
#1
Cheryl Li, Satoshi Shoji, Jean Beebe
AIMS: The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included...
May 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29775966/an-enigmatic-case-presentation-of-budd-chiari-syndrome-with-pulmonary-embolism-an-unusual-syndrome-with-an-uncommon-complication
#2
A M Al-Sharydah, A H Al-Abdulwahhab, H A Abu AlOla
INTRODUCTION: In patients with a hypercoagulable state, such as patients with pulmonary embolism and/or Budd-Chiari syndrome, the complications from multiple gene mutations are more numerous than those from a single mutation. The authors present a woman with no major prior medical history who presented with pulmonary embolism and Budd-Chiari syndrome; this enigmatic co-occurrence has never been solely reported without underlying aetiology in a patient without prior medical conditions...
May 3, 2018: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29775896/dysregulated-network-of-mirnas-involved-in-the-pathogenesis-of-multiple-sclerosis
#3
REVIEW
Sanam Dolati, Faroogh Marofi, Zohreh Babaloo, Leili Aghebati-Maleki, Leila Roshangar, Majid Ahmadi, Reza Rikhtegar, Mehdi Yousefi
Multiple sclerosis (MS) is a chronic and organ-specific autoimmune disease in which immune cells act against the myelin sheath, resulting in central nervous system (CNS) damage. It has been revealed that miRNAs can play significant role in the pathogenesis of MS. These regulatory molecules lead to the activation of different signaling pathways, regulation of several transcriptional factors, influencing the differentiation of Th17 cells, development of Tregs and alteration from Th2 to Th1 response in MS. New studies have discovered that dysregulation of miRNAs may trigger abnormal immune responses leading consequently in the emergence of autoimmunity...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775619/proteomic-approach-to-profiling-immune-complex-antigens-in-cerebrospinal-fluid-samples-from-patients-with-central-nervous-system-autoimmune-diseases
#4
Nozomi Aibara, Kunihiro Ichinose, Miyako Baba, Hideki Nakajima, Katsuya Satoh, Ryuichiro Atarashi, Naoya Kishikawa, Noriyuki Nishida, Atsushi Kawakami, Naotaka Kuroda, Kaname Ohyama
BACKGROUND: Immune complexes (ICs) may clearly reflect immunological abnormalities caused by disease, especially for autoimmune diseases. Although ICs have been detected in cerebrospinal fluid (CSF) from patients with CNS autoimmune diseases, identities of antigens in such ICs have not been comprehensively determined. METHODS: We used immune complexome analysis, in which nano-liquid chromatography-tandem mass spectrometry is employed to comprehensively identify antigens incorporated into ICs in biological fluids, to characterize ICs in CSF samples from patients with CNS autoimmune diseases, and to find disease-specific IC antigen to a certain CNS autoimmune disease...
May 15, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29775441/-the-biological-function-and-significance-of-il-35-in-the-pathogenesis-of-atherosclerosis
#5
EDITORIAL
Mateusz Staciwa, Marlena Broncel
The imbalance of anti-inflammatory /pro- inflammatory cytokines plays an important role in the progression of atherosclerosis. Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBVinduced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immunesuppressive cytokine mainly produced by regulatory T cells. Accumulating evidence suggests that IL-35 may represent a target for antiatherosclerotic therapy based on its several anti-inflammatory features. This review provide a brief overview of IL-35 biology and the role of IL-35 in the atherosclerosis, autoimmune disease and cancers...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29775210/the-effect-of-simulated-space-radiation-on-the-n-glycosylation-of-human-immunoglobulin-g1
#6
Mate Szarka, Szabolcs Szilasi, Boglarka Donczo, Daniel Sarkozy, Istvan Rajta, Andras Guttman
On a roundtrip to Mars, astronauts are expectedly exposed to an approximate amount of radiation that exceeds the lifetime limits on Earth. This elevated radiation dose is mainly due to Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE). Specific patterns of the N-glycosylation of human immunoglobulins have already been associated with various ailments such as autoimmune diseases, malignant transformation, chronic inflammation and ageing. The focus of our work was to investigate the effect of low-energy proton irradiation on the IgG N-glycosylation profile with the goal if disease associated changes could be detected during space travel and not altered by space radiation...
May 18, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29774953/dermoscopic-patterns-of-filiform-papillae-of-the-tongue-in-patients-with-and-without-connective-tissue-autoimmune-diseases
#7
José Manuel Díaz-González, María E Vega-Memije, Adalberto Mosqueda-Taylor, Víctor Noé García-Edgar, Juan Carlos Cuevas-González
BACKGROUND: Connective tissue autoimmune diseases (CTADs) constitute a group of conditions, including rheumatoid arthritis; systemic lupus erythematosus; mixed connective tissue disease; calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome; scleroderma; dermatomyositis; and Sjögren syndrome. There are few studies on the alterations in filiform papillae in CTAD. Thus, the objective of this work was to determine whether there are changes in the macroscopic and dermoscopic patterns of filiform papillae...
May 18, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29774846/occupation-associated-fatal-limbic-encephalitis-caused-by-variegated-squirrel-bornavirus-1-germany-2013
#8
Dennis Tappe, Kore Schlottau, Daniel Cadar, Bernd Hoffmann, Lorenz Balke, Burkhard Bewig, Donata Hoffmann, Philip Eisermann, Helmut Fickenscher, Andi Krumbholz, Helmut Laufs, Monika Huhndorf, Maria Rosenthal, Walter Schulz-Schaeffer, Gabriele Ismer, Sven-Kevin Hotop, Mark Brönstrup, Anthonina Ott, Jonas Schmidt-Chanasit, Martin Beer
Limbic encephalitis is commonly regarded as an autoimmune-mediated disease. However, after the recent detection of zoonotic variegated squirrel bornavirus 1 in a Prevost's squirrel (Callosciurus prevostii) in a zoo in northern Germany, we retrospectively investigated a fatal case in an autoantibody-seronegative animal caretaker who had worked at that zoo. The virus had been discovered in 2015 as the cause of a cluster of cases of fatal encephalitis among breeders of variegated squirrels (Sciurus variegatoides) in eastern Germany...
June 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#9
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29774578/the-immunobiology-of-rankl-and-myeloid-derived-suppressor-cell-activation-in-igg4-related-sclerosing-cholangitis
#10
Min Lian, Qixia Wang, Xiang Jiang, Jun Zhang, Yiran Wei, Yanmei Li, Bo Li, Weihua Chen, Haiyan Zhang, Qi Miao, Yanshen Peng, Xiao Xiao, Li Sheng, Weici Zhang, Jingyuan Fang, Ruqi Tang, M Eric Gershwin, Xiong Ma
The primary function of myeloid derived suppressor cells (MDSCs) is reflected in their immune modulatory role in several immune-mediated diseases. In IgG4-related disease (IgG4-RD), it has been hypothesized that there are selective regulatory defects that lead to a Th2 bias immune response. Herein we have taken advantage of a large cohort of patients with IgG4-related sclerosing cholangitis (IgG4-SC), the most common extra-pancreatic involvement of IgG4-RD, as well as controls consisting of primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and healthy volunteers, to study MDSC...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29774506/therapeutic-potential-of-mesenchymal-stem-cell-derived-exosomes-in-the-treatment-of-eye-diseases
#11
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Nebojsa Arsenijevic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases...
May 18, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29774057/ocrelizumab-a-new-milestone-in-multiple-sclerosis-therapy
#12
REVIEW
Patricia Mulero, Luciana Midaglia, Xavier Montalban
B cells play a central role in the pathogenesis of multiple sclerosis (MS): they are involved in the activation of pro-inflammatory T cells, secretion of pro-inflammatory cytokines and production of autoantibodies directed against myelin. Hence, the use of B cell-depleting monoclonal antibodies as therapy for autoimmune diseases, including MS, has increased in recent years. Previous results with rituximab, the first therapeutic B cell-depleting chimeric monoclonal antibody that showed efficacy in MS clinical trials, encouraged researchers to evaluate the efficacy of a humanized anti-CD20 antibody, ocrelizumab, in MS...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#13
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774031/il-10-producing-b-cells-ability-to-induce-regulatory-t-cells-is-maintained-in-rheumatoid-arthritis
#14
Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, Claire Daien
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+ cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774029/lfa-1-in-t-cell-migration-and-differentiation
#15
REVIEW
Brandon L Walling, Minsoo Kim
Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774027/clinical-remission-of-sight-threatening-non-infectious-uveitis-is-characterized-by-an-upregulation-of-peripheral-t-regulatory-cell-polarized-towards-t-bet-and-tigit
#16
Rose M Gilbert, Xiaozhe Zhang, Robert D Sampson, Michael R Ehrenstein, Dao X Nguyen, Mahid Chaudhry, Charles Mein, Nadiya Mahmud, Grazyna Galatowicz, Oren Tomkins-Netzer, Virginia L Calder, Sue Lightman
Background: Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4+ CD25+ FoxP3+ T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774024/quantification-of-hla-dm-dependent-major-histocompatibility-complex-of-class-ii-immunopeptidomes-by-the-peptide-landscape-antigenic-epitope-alignment-utility
#17
Miguel Álvaro-Benito, Eliot Morrison, Esam T Abualrous, Benno Kuropka, Christian Freund
The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773813/amelioration-of-experimental-autoimmune-encephalomyelitis-and-dss-induced-colitis-by-ntg-a-009-through-the-inhibition-of-th1-and-th17-cells-differentiation
#18
Suman Acharya, Maheshwor Timilshina, Liyuan Jiang, Sabita Neupane, Dong-Young Choi, Sang Won Park, Sang Yeul Lee, Byeong-Seon Jeong, Jung-Ae Kim, Tae-Gyu Nam, Jae-Hoon Chang
CD4+ T cells are the central for the mammalian adaptive immune system. Naïve CD4+ T cells mainly differentiate in to pro-inflammatory Th1, Th2 and Th17 cells upon antigenic stimulation. IFN-γ secreting Th1 cells and IL-17 secreting Th17 cells are found to play key roles in autoimmune diseases like multiple sclerosis (MS) and ulcerative colitis (UC). In this study we found NTG-A-009, 6-aminopyridin-3-ol, has great inhibitory effect on in vitro differentiation of Th1 and Th17 cells without affecting regulatory T cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773681/decreased-expression-of-circulating-aire-and-increased-tfh-tfr-cells-in-myasthenia-gravis-patients
#19
Sijia Zhao, Jiaqi Ding, Shengyuan Wang, Chuan Li, Peng Guo, Min Zhang, Zhuyi Li
Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of Autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells(we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T follicular helper (cTfh) and T follicular regulatory (cTfr) cells in MG patients...
May 17, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29773643/the-transcription-factor-bhlhe40-is-a-switch-of-inflammatory-versus-antiinflammatory-th1-cell-fate-determination
#20
Fang Yu, Suveena Sharma, Dragana Jankovic, Rama Krishna Gurram, Pan Su, Gangqing Hu, Rao Li, Sadiye Rieder, Keji Zhao, Bing Sun, Jinfang Zhu
Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-γ; some Th1 cells can also be antiinflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40 -deficient CD4 Th1 cells produced less IFN-γ but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo...
May 17, 2018: Journal of Experimental Medicine
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