DOCSLIB.ORG

CXCL10 Could Drive Longer Duration of Mechanical Ventilation During COVID-19 ARDS

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
CXCL10 Could Drive Longer Duration of Mechanical Ventilation During COVID-19 ARDS Blot et al. Critical Care (2020) 24:632 https://doi.org/10.1186/s13054-020-03328-0 RESEARCH Open Access CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS Mathieu Blot1,2*, Marine Jacquier2,9, Ludwig-Serge Aho Glele10, Guillaume Beltramo3, Maxime Nguyen2,4, Philippe Bonniaud3, Sebastien Prin9, Pascal Andreu9, Belaid Bouhemad2,4, Jean-Baptiste Bour5, Christine Binquet6, Lionel Piroth1,6, Jean-Paul Pais de Barros2,7, David Masson2,8, Jean-Pierre Quenot2,6,9, Pierre-Emmanuel Charles2,9 and Pneumochondrie study group Abstract Background: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). Methods: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. Results: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL- 10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations. Conclusion: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. Trial registration: ClinicalTrials.gov, NCT03955887 Keywords: Acute respiratory distress syndrome, COVID-19, SARS-CoV-2, Mechanical ventilation, Immune response, Bronchoalveolar lavage, CXCL10, Mitochondrial DNA, Biomarker * Correspondence: [email protected] 1Infectious Diseases Department, Dijon Bourgogne University Hospital, Dijon, France 2INSERM, LNC UMR 1231, FCS Bourgogne-Franche Comté, LipSTIC LabEx, F-21000 Dijon, France Full list of author information is available at the end of the article © The Author(s). 2020, corrected publication 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Blot et al. Critical Care (2020) 24:632 Page 2 of 15 Background the department of pneumology at the University Hospital of Since December 2019, the world is experiencing an out- Dijon (France). Patients were eligible if a BAL was considered break of coronavirus disease 2019 (COVID-19) caused necessary by the attending physician and if they had (1) pneu- by severe acute respiratory syndrome coronavirus 2 monia (≥ 2 acute signs including cough, purulent sputum, (SARS-CoV-2). Clinical, radiological, and biological dif- dyspnea, chest pain, temperature < 35 °C or ≥ 38.5 °C, and ferences have been found between COVID-19-related novel radiological pulmonary infiltrate); (2) ARDS (according acute respiratory distress syndrome (ARDS) and ARDS to the Berlin Definition) [12]; (3) requiring mechanical venti- from another origin. Indeed, the sudden clinical deteri- lation (MV); and (4) BAL was performed within 72 h of the oration observed 1 week after symptom onset, together start of MV. COVID-19 ARDS patients were eligible if they with deep hypoxemia contrasting with “normal” (> 40 tested positive for SARS-CoV-2 by reverse transcriptase poly- mL/cmH2O) lung compliance, and the higher incidence merase chain reaction (RT-PCR) for at least one respiratory of thromboembolic events suggest that SARS-CoV-2 is sample. The control population consisted of outpatients with- driven by a unique pathogenesis resulting in an atypical out fever during the last 15 days, not under mechanical venti- form of ARDS [1, 2]. Notably, mechanical ventilation ap- lation, and undergoing a BAL for a condition not related to pears to be required for twice as long in COVID-19 than acute infection (evaluation of a pulmonary nodule, chronic in non-COVID-19 ARDS patients [3, 4]. interstitial syndrome, or unexplained chronic pulmonary It has been established that the virus invades type 2 alveo- sign). Seven control patients and 7 bacterial ARDS patients lar cells and ciliated epithelial cells that express ACE2 [5]. were prospectively included between June 11, 2019, and Janu- Subsequently, as they die, infected cells release virus parti- ary 20, 2020 (5 weeks before the pandemic COVID-19 started cles and intracellular components including molecules in Burgundy, France). Fourteen COVID-19 ARDS patients likely to act as alarmins (i.e., danger signals), as reflected by were included between March 30 and April 09, 2020. Oral rising lactate dehydrogenase (LDH) levels in the plasma [6]. consent was obtained from the patients or their legal repre- The ensuing recruitment and activation of immune cells sentatives. Approval was obtained from the ethics committee lead to lung damage [7]. For now, several studies have (Comité de Protection des Personnes Sud-Est III; 2018-035 B), established that the hyperinflammatory response (namely and an amendment was obtained to include supplementary the cytokine storm) induced by SARS-CoV-2 is associated patients with COVID-19-related ARDS. with disease severity and could contribute to the develop- ment of ARDS [8, 9]. In addition, since most patients need to undergo mechanical ventilation in this context, Variables of interest, clinical outcomes, and data ventilator-induced lung injury (VILI) could exacerbate tis- collection sue damage as well as local and systemic inflammation, Demographic data, comorbidities, clinical and bio- thus acting as a “second hit.” Our team has previously logical parameters, and severity scores (Sequential shown that mitochondrial alarmins (i.e., mitochondrial Organ Failure Assessment (SOFA) [13]andthenew DNA) are released by human epithelial cells submitted to simplified acute physiology score (SAPS II) [14]) were cyclic stretch, and these alarmins are also recovered from calculated on the first day of ARDS. Septic shock was bronchoalveolar lavage (BAL) fluid obtained from either defined as persistent hypotension requiring vasopres- ventilated rabbits or ARDS patients. By promoting chemo- sors and a serum lactate level > 2 mmol/L despite ad- taxis and activation of polymorphonuclear neutrophils equate volume resuscitation. Clinical outcomes were (PMNs), mitochondrial alarmins are thought to represent recorded up to 30 days after the start of ARDS: 30-day proximal endogenous mediators of VILI and ARDS when mortality; number of hospital-, ICU-, and ventilator- they are released by injured alveolar cells [10, 11]. free days; and hospital-acquired complications (ventila- The aim of our study was to compare cytokine response tory-acquired pneumonia (VAP), thrombo-embolic dis- patterns, in both alveolar and systemic compartments, be- ease). The “ventilator-free days” outcome was defined tween COVID-19-related ARDS and non-COVID-19-re- as the number of days alive from day 1 of ARDS to day lated ARDS (i.e., ARDS complicating pneumonia from 30 during which the patient was breathing without MV. another origin). In addition, we sought to establish the ex- Dedicated clinical research assistants collected all data tent to which the immune signature could be associated using a standardized electronic case report form. Auto- with clinical evolution according to ARDS etiology. matic checks were generated for missing or incoherent data. All abnormal data were controlled by a physician- Methods scientist. Study design and patient selection The concentration of inflammatory cytokines and This is an ancillary study of the ongoing prospective PNEU- mitochondrial alarmins (cell-free mitochondrial DNA MOCHONDRIE study (ClinicalTrials.gov NCT03955887) concentrations) was measured within both the systemic which started in June 2019
Load more

Recommended publications
  • Clinical Reasoning
    RESIDENT & FELLOW SECTION Clinical Reasoning: Section Editor A 49-year-old woman with progressive Mitchell S.V. Elkind, MD, MS motor deficit Ana Monteiro, MD SECTION 1 strength, and difficulty protruding the tongue, without Amélia Mendes, MD A previously healthy 49-year-old woman presented with fasciculations or atrophy. Symmetrical tetraparesis Fernando Silveira, MD progressive motor deficit. The complaints started the (proximal-greater-than-distal weakness) and increased Lígia Castro, MD year before with weakness of the right arm. Over the tone were noted, with severe pain upon mobilization Goreti Nadais, MD subsequent months, she developed weakness in the left and palpation of joints and muscles. Deep tendon reflexes arm, followed by both legs, and, finally, difficulty speak- were brisk and symmetric, with bilateral flexor plantar ing, with nasal voice, and swallowing. It was increasingly responses. There was atrophy of the interosseous muscles Correspondence to difficult to attend to her chores, and, by the time she of the hands and shoulder girdle muscle wasting. Dr. Monteiro: sought medical attention, she needed help with all daily [email protected] Questions for consideration: activities. In the last few weeks, she also complained of diffuse joint and muscle pain. Medical and family history 1. How do you localize the symptoms: upper motor were unremarkable. neuron (UMN) or lower motor neuron (LMN), Neurologic examination showed bilateral facial weak- neuromuscular junction (NMJ), peripheral nerve, ness, severe dysarthria, dysphonia and dysphagia (nau- or muscle? What is the broad differential? seous reflex preserved), decreased shoulder elevation 2. What findings on examination would be helpful? GO TO SECTION 2 Supplemental data at Neurology.org From the Departments of Neurology (A.
    [Show full text]
  • An Overview of Various Diagnostic Methods to Detect Antinuclear Antibodies of Connective Tissue Diseases
    DOI: 10.7860/NJLM/2021/48042:2492 Review Article An Overview of Various Diagnostic Methods to Detect Antinuclear Antibodies of Microbiology Section Microbiology Connective Tissue Diseases SAIKEERTHANA DURAISAMY ABSTRACT Antinuclear Antibodies (ANA) are present in many autoimmune disorders and these disorders are collectively called as Connective Tissue Diseases (CTD). There are various CTDs which include Systemic Lupus Erythematosus (SLE), Sjogren’s syndrome, Systemic Sclerosis (SS), Inflammatory Myositis (IM), Mixed Connective Tissue Disorder (MCTD) and Rheumatoid Arthritis (RA). Detection of ANAs in these CTDs is highly sensitive and is of utmost importance. The ANAs specific to SLE includes antidouble stranded Deoxyribonucleic Acid (antidsDNA), single stranded DNA (ssDNA). Scleroderma or Systemic Sclerosis (SS) is an immune mediated rheumatic disease where autoantibodies like topoisomerase 1, Ribonucleic Acid (RNA) polymerase 1 and fibrillarin are useful in diagnosis. Idiopathic Inflammatory Myositis (IIM) such as polymyositis and dermatomyositis are characterised by the presence of autoantibodies like PM-scl (Polymyositis-Scleromyositis), Mi-1 (Myositis specific autoantibody found in idiopathic inflammatory myositis), Mi-2 and Ku (DNA Binding Protein in dermatomyositis). Antibody titres against polypeptides on the U1 Ribonucleoprotein (U1RNP) is useful in the detection mixed CTD. Sjogren’s syndrome is characterised by the presence of serum autoantibodies against two ribonucleoproteinic complexes like Ro/SSA (Extractable nuclear antigen found in Sjogren's syndrome related antigen A auto antibodies) and La/SSB (Extractable nuclear antigen found in Sjogren's syndrome or lupus erythematous). ANA analysis can be done by techniques like indirect immunofluorescence method, Enzyme Linked Immuno Sorbent Assay (ELISA), Immunoprecipitation in agar and western blotting. All these diagnostic methods give precise identification of these antibodies with high accuracy.
    [Show full text]
  • The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature
    International Journal of Molecular Sciences Review The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature Jan Korbecki 1 , Klaudyna Kojder 2, Patrycja Kapczuk 1, Patrycja Kupnicka 1 , Barbara Gawro ´nska-Szklarz 3 , Izabela Gutowska 4 , Dariusz Chlubek 1 and Irena Baranowska-Bosiacka 1,* 1 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] (J.K.); [email protected] (P.K.); [email protected] (P.K.); [email protected] (D.C.) 2 Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-281 Szczecin, Poland; [email protected] 3 Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] 4 Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wlkp. 72 Av., 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-914661515 Abstract: Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influ- ence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 Citation: Korbecki, J.; Kojder, K.; Kapczuk, P.; Kupnicka, P.; (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors— Gawro´nska-Szklarz,B.; Gutowska, I.; CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8.
    [Show full text]
  • The Chemokine System in Innate Immunity
    Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press The Chemokine System in Innate Immunity Caroline L. Sokol and Andrew D. Luster Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114 Correspondence: [email protected] Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. Theyalso recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses. hemokines are chemotactic cytokines that with emphasis placed on its role in the innate Ccontrol cell migration and cell positioning immune system. throughout development, homeostasis, and in- flammation. The immune system, which is de- pendent on the coordinated migration of cells, CHEMOKINES AND CHEMOKINE RECEPTORS is particularly dependent on chemokines for its function.
    [Show full text]
  • Starvation and Antimetabolic Therapy Promote Cytokine Release and Recruitment of Immune Cells
    Starvation and antimetabolic therapy promote cytokine release and recruitment of immune cells Franziska Püschela, Francesca Favaroa,b,c,d,1, Jaime Redondo-Pedrazaa,1, Estefanía Lucendoa, Raffaella Iurlaroa, Sandrine Marchettie, Blanca Majema, Eric Elderingb,c,d, Ernest Nadalf, Jean-Ehrland Riccie, Eric Chevetg,h, and Cristina Muñoz-Pinedoa,i,2 aOncobell Program, Bellvitge Biomedical Research Institute, Hospitalet, 08908 Barcelona, Spain; bDepartment of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; cLymphoma and Myeloma Center, Cancer Center Amsterdam, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; dAmsterdam Institute for Infection & Immunity, 1105 AZ Amsterdam, The Netherlands; eINSERM, Centre Méditerranéen de Médecine Moléculaire, Université Côte d’Azur, 06204 Nice, France; fThoracic Oncology Unit, Department of Medical Oncology, Catalan Institute of Oncology, Hospitalet, 08908 Barcelona, Spain; gINSERM U1242 “Chemistry, Oncogenesis, Stress, Signaling,” Université de Rennes, 35042 Rennes, France; hINSERM U1242, Centre de Lutte Contre le Cancer Eugène Marquis, 35042 Rennes, France; and iDepartment of Basic Nursing, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Hospitalet, 08907 Barcelona, Spain Edited by Karen H. Vousden, Francis Crick Institute, London, United Kingdom, and approved March 16, 2020 (received for review August 14, 2019) Cellular starvation is typically a consequence of tissue injury that of oxygen or nutrients. However, some reports suggest that nutrient disrupts the local blood supply but can also occur where cell restriction, even without cell death, can be sufficient to promote the populations outgrow the local vasculature, as observed in solid synthesis and/or secretion of select proinflammatory cytokines tumors. Cells react to nutrient deprivation by adapting their (7–9).
    [Show full text]
  • Critical Role of CXCL4 in the Lung Pathogenesis of Influenza (H1N1) Respiratory Infection
    ARTICLES Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection L Guo1,3, K Feng1,3, YC Wang1,3, JJ Mei1,2, RT Ning1, HW Zheng1, JJ Wang1, GS Worthen2, X Wang1, J Song1,QHLi1 and LD Liu1 Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. Additionally, CXCL4 deficiency decreased leukocyte accumulation in the infected lung with markedly decreased neutrophil infiltration into the lung during early infection and extensive leukocyte, especially lymphocyte accumulation at the late infection stage. Loss of CXCL4 did not affect the activation of adaptive immune T and B lymphocytes during the late stage of lung infection. Further study revealed that CXCL4 deficiency inhibited neutrophil recruitment to the infected mouse lung. Thus the above results identify CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung. INTRODUCTION necrosis factor (TNF)-a, interleukin (IL)-6, and IL-1b, to exert Influenza A virus (IAV) infections cause respiratory diseases in further antiviral innate immune effects.2 Meanwhile, the innate large populations worldwide every year and result in seasonal immune cells act as antigen-presenting cells and release influenza epidemics and unexpected pandemic.
    [Show full text]
  • Autoantibodies in Systemic Autoimmune Diseases K
    umschlag_neutral.qxd 03.10.2007 10:53 Seite 1 2nd edition Karsten Conrad, Werner Schößler, Falk Hiepe, Marvin J. Fritzler Autoantibodies are a very heterogeneous group of antibodies with respect to their specificity, induction, effects, and clinical signifi- cance. Testing for autoantibodies can be helpful or necessary for the diagnosis, differential diagnosis, prognostication, or monitoring of Autoantibodies in Systemic autoimmune diseases. In case of limited (forme fruste) disease or a single disease manifestation, the detection of serum autoantibodies can play an Autoimmune Diseases important role in raising the suspicion of evolving disease and forecasting prog- nosis. This book and reference guide is intended to assist the physician in under- A Diagnostic Reference standing and interpreting the variety of autoantibodies that are being used as diagnostic and prognostic tools for patients with systemic rheumatic diseases. Autoantibodies observed in systemic autoimmune diseases are described in alphabetical order in Part 1 of this reference guide. In Part 2, systemic autoim- mune disorders as well as symptoms that indicate the possible presence of an autoimmune disease are listed. Systemic manifestations of organ-specific autoim- mune diseases will not be covered in this volume. Guide marks were inserted to K. Conrad, W.K. Conrad, Hiepe, M. J. Fritzler F. Schößler, ensure fast and easy cross-reference between symptoms, a given autoimmune disease and associated autoantibodies. Although the landscape of autoantibody testing continues to change, this information will be a useful and valuable refer- ence for many years to come. AUTOANTIGENS, AUTOANTIBODIES, AUTOIMMUNITY Autoantibodies in Systemic Autoimmune Diseases Autoimmune in Systemic Autoantibodies Volume 2, second Edition – 2007 ISBN 978-3-89967-420-0 www.pabst-publishers.com PABST Autoantibodies in Systemic Autoimmune Diseases A Diagnostic Reference Karsten Conrad, Werner Schößler, Falk Hiepe, Marvin J.
    [Show full text]
  • Exploration of Prognostic Biomarkers and Therapeutic Targets in the Microenvironment of Bladder Cancer Based on CXC Chemokines
    Exploration of Prognostic Biomarkers and Therapeutic Targets in The Microenvironment of Bladder Cancer Based on CXC Chemokines Xiaoqi Sun Department of Urology, Kaiping Central Hospital, Kaiping, 529300, China Qunxi Chen Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China Lihong Zhang Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China Jiewei Chen Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China Xinke Zhang ( [email protected] ) Sun Yat-sen University Cancer Center Research Keywords: Bladder cancer, Biomarkers, CXC Chemokines, Microenvironment Posted Date: February 24th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-223127/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/29 Abstract Background: Bladder cancer (BLCA) has a high rate of morbidity and mortality, and is considered as one of the most malignant tumors of the urinary system. Tumor cells interact with surrounding interstitial cells, playing a key role in carcinogenesis and progression, which is partly mediated by chemokines. CXC chemokines exert anti‐tumor biological roles in the tumor microenvironment and affect patient prognosis. Nevertheless, their expression and prognostic values patients with BLCA remain unclear. Methods: We used online tools, including Oncomine, UALCAN, GEPIA, GEO databases, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRUST (version 2.0), LinkedOmics, TCGA, and TIMER2.0 to perform the relevant analysis. Results: The mRNA levels of C-X-C motif chemokine ligand (CXCL)1, CXCL5, CXCL6, CXCL7, CXCL9, CXCL10, CXCL11, CXCL13, CXCL16, and CXCL17 were increased signicantly increased, and those of CXCL2, CXCL3, and CXCL12 were decreased signicantly in BLCA tissues as assessed using the Oncomine, TCGA, and GEO databases.
    [Show full text]
  • That Are Not Lielu Uutuullittu
    THAT ARE NOT LIELUUS009987356B2 UUTUULLITTU (12 ) United States Patent ( 10 ) Patent No. : US 9 ,987 , 356 B2 Reimann et al. ( 45) Date of Patent : Jun . 5 , 2018 (54 ) ANTI -CD40 ANTIBODIES AND METHODS 762 A 12 / 1997 Queen et al. 5 , 801, 227 A 9 / 1998 Fanslow , III et al. OF ADMINISTERING THEREOF 5 , 874 ,082 A 2 / 1999 de Boer 6 ,004 , 552 A 12 / 1999 de Boer et al. ( 75 ) Inventors: Keith A . Reimann , Marblehead , MA 6 ,051 ,228 A 4 / 2000 Aruffo et al. (US ) ; Rijian Wang , Saugus, MA (US ) ; 6 ,054 ,297 A 4 / 2000 Carter et al . Christian P . Larsen , Atlanta , GA (US ) 6 ,056 , 959 A 5 /2000 de Boer et al. 6 , 132 , 978 A 10 /2000 Gelfand et al. 6 , 280 , 957 B18 / 2001 Sayegh et al. ( 73) Assignees : Beth Israel Deaconess Medical 6 , 312 ,693 B1 11/ 2001 Aruffo et al. Center , Inc ., Boston , MA (US ) ; Emory 6 , 315 , 998 B111 / 2001 de Boer et al. University , Atlanta , GA (US ) 6 , 413 ,514 B1 7 / 2002 Aruffo et al. 6 , 632, 927 B2 10 /2003 Adair et al. ( * ) Notice : Subject to any disclaimer , the term of this 7 ,063 , 845 B2 6 / 2006 Mikayama et al. patent is extended or adjusted under 35 7 , 193 , 064 B2 3 / 2007 Mikayama et al. 7 , 288 , 251 B2 10 / 2007 Bedian et al . U . S . C . 154 ( b ) by 464 days . 7 , 361 , 345 B2 4 /2008 de Boer et al. 7 , 445 , 780 B2 11/ 2008 Chu et al. (21 ) Appl . No.
    [Show full text]
  • Role of Chemokines in Hepatocellular Carcinoma (Review)
    ONCOLOGY REPORTS 45: 809-823, 2021 Role of chemokines in hepatocellular carcinoma (Review) DONGDONG XUE1*, YA ZHENG2*, JUNYE WEN1, JINGZHAO HAN1, HONGFANG TUO1, YIFAN LIU1 and YANHUI PENG1 1Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051; 2Medical Center Laboratory, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, P.R. China Received September 5, 2020; Accepted December 4, 2020 DOI: 10.3892/or.2020.7906 Abstract. Hepatocellular carcinoma (HCC) is a prevalent 1. Introduction malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges Hepatocellular carcinoma (HCC) is the sixth most common for the treatment of HCC is the prevention or management type of cancer worldwide and the third leading cause of of recurrence and metastasis of HCC. It has been found that cancer-associated death (1). Most patients cannot undergo chemokines and their receptors serve a pivotal role in HCC radical surgery due to the presence of intrahepatic or distant progression. In the present review, the literature on the multi- organ metastases, and at present, the primary treatment methods factorial roles of exosomes in HCC from PubMed, Cochrane for HCC include surgery, local ablation therapy and radiation library and Embase were obtained, with a specific focus on intervention (2). These methods allow for effective treatment the functions and mechanisms of chemokines in HCC. To and management of patients with HCC during the early stages, date, >50 chemokines have been found, which can be divided with 5-year survival rates as high as 70% (3). Despite the into four families: CXC, CX3C, CC and XC, according to the continuous development of traditional treatment methods, the different positions of the conserved N-terminal cysteine resi- issue of recurrence and metastasis of HCC, causing adverse dues.
    [Show full text]
  • B-Cell Development, Activation, and Differentiation
    B-Cell Development, Activation, and Differentiation Sarah Holstein, MD, PhD Nov 13, 2014 Lymphoid tissues • Primary – Bone marrow – Thymus • Secondary – Lymph nodes – Spleen – Tonsils – Lymphoid tissue within GI and respiratory tracts Overview of B cell development • B cells are generated in the bone marrow • Takes 1-2 weeks to develop from hematopoietic stem cells to mature B cells • Sequence of expression of cell surface receptor and adhesion molecules which allows for differentiation of B cells, proliferation at various stages, and movement within the bone marrow microenvironment • Immature B cell leaves the bone marrow and undergoes further differentiation • Immune system must create a repertoire of receptors capable of recognizing a large array of antigens while at the same time eliminating self-reactive B cells Overview of B cell development • Early B cell development constitutes the steps that lead to B cell commitment and expression of surface immunoglobulin, production of mature B cells • Mature B cells leave the bone marrow and migrate to secondary lymphoid tissues • B cells then interact with exogenous antigen and/or T helper cells = antigen- dependent phase Overview of B cells Hematopoiesis • Hematopoietic stem cells (HSCs) source of all blood cells • Blood-forming cells first found in the yolk sac (primarily primitive rbc production) • HSCs arise in distal aorta ~3-4 weeks • HSCs migrate to the liver (primary site of hematopoiesis after 6 wks gestation) • Bone marrow hematopoiesis starts ~5 months of gestation Role of bone
    [Show full text]
  • Autoantibodies and Anti-Microbial Antibodies
    bioRxiv preprint doi: https://doi.org/10.1101/403519; this version posted August 29, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Autoantibodies and anti-microbial antibodies: Homology of the protein sequences of human autoantigens and the microbes with implication of microbial etiology in autoimmune diseases Peilin Zhang, MD., Ph.D. PZM Diagnostics, LLC Charleston, WV 25301 Correspondence: Peilin Zhang, MD., Ph.D. PZM Diagnostics, LLC. 500 Donnally St., Suite 303 Charleston, WV 25301 Email: [email protected] Tel: 304 444 7505 1 bioRxiv preprint doi: https://doi.org/10.1101/403519; this version posted August 29, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Abstract Autoimmune disease is a group of diverse clinical syndromes with defining autoantibodies within the circulation. The pathogenesis of autoantibodies in autoimmune disease is poorly understood. In this study, human autoantigens in all known autoimmune diseases were examined for the amino acid sequences in comparison to the microbial proteins including bacterial and fungal proteins by searching Genbank protein databases. Homologies between the human autoantigens and the microbial proteins were ranked high, medium, and low based on the default search parameters at the NCBI protein databases. Totally 64 human protein autoantigens important for a variety of autoimmune diseases were examined, and 26 autoantigens were ranked high, 19 ranked medium to bacterial proteins (69%) and 27 ranked high and 16 ranked medium to fungal proteins (66%) in their respective amino acid sequence homologies.
    [Show full text]