DOCSLIB.ORG

New Methods for Characterization of N-Type Glycosylation of Proteins by Integration of LC-MS/MS and NMR

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
New Methods for Characterization of N-Type Glycosylation of Proteins by Integration of LC-MS/MS and NMR New Methods for Characterization of N-type Glycosylation of Proteins by Integration of LC-MS/MS and NMR Thesis Submitted in fulfillment of the requirements of the degree Doctor rer. nat. at the Department of Chemistry, Faculty of Sciences, University of Hamburg by Alena Wiegandt from Hamburg Hamburg, 2016 This thesis was prepared at the Institute for Organic Chemistry from October 2012 to July 2016 (managing director: Prof. Dr. C.B.W. Stark). I would like to thank Prof. Dr. Bernd Meyer for his continuous and motivating support during the work on my PhD thesis. I would like to thank Prof. Dr. Dr. h. c. mult. Wittko Francke for being the second reviewer of this thesis. 1st Reviewer: Prof. Dr. Bernd Meyer 2nd Reviewer: Prof. Dr. Dr. h.c. mult. Wittko Francke Date of defense: 07.04.2017 OUTLINE Outline ABBREVIATIONS ..................................................................................................................... VIII 1 SUMMARY ............................................................................................................................ 1 2 ZUSAMMENFASSUNG .......................................................................................................... 4 3 INTRODUCTION ................................................................................................................... 7 3.1 Glycosylation of Proteins - Biosynthesis, Structures, Functions .................................... 8 3.2 Glycans in Human Diseases .......................................................................................... 10 Potential of Glycans as Specific Biomarkers for Human Diseases ...................... 11 Limits of Glyco-Based Biopharmaceuticals - Quality Control ............................ 13 3.3 Analytics of Protein Glycosylation ............................................................................... 14 4 OBJECTIVE ........................................................................................................................ 19 5 RESULTS AND DISCUSSION ............................................................................................... 20 5.1 Glycosylation of Biopharmaceuticals ........................................................................... 20 Three-Dimensional Cross Correlation of Cetuximab ........................................... 22 Glycosylation Analysis on the Level of Intact Proteins ....................................... 38 Interlaboratory Study on Glycan Analysis ........................................................... 59 5.2 Histidine-Rich Glycoprotein ......................................................................................... 71 Development of a Purification Strategy for HRG from Human Blood Plasma ... 72 Mass Spectrometric Analysis of Histidine-Rich Glycoprotein ............................ 79 5.3 Prolactin-Inducible Protein ........................................................................................... 86 Structural Analysis of the N-Glycosylation of Human Salivary PIP ................... 87 Enrichment of Prolactin-Inducible Protein from Human Saliva .......................... 99 Nonsynonymous Single Nucleotide Polymorphism in Salivary PIP ................. 103 Comparison of the N-Glycosylation of Salivary PIP from Healthy Individuals 107 N-Glycosylation of Salivary PIP during Pregnancy ........................................... 128 Comparative Study of N-Glycosylation of Salivary PIP between Breast ............... Cancer Patients and Healthy Donors .................................................................. 129 V OUTLINE 6 EXPERIMENTAL PROCEDURES ....................................................................................... 132 6.1 Instruments, Material and Software ............................................................................ 132 6.2 Analysis of Released N-Glycans of Cetuximab .......................................................... 133 N-Glycan Release from Cetuximab and Purification ......................................... 133 Chromatographic Separation, Mass Spectrometric Analysis and Fractionation ...... of Released N-Glycans from Cetuximab by PGC-LC-ESI-q/TOF ..................... 134 1H-NMR Analysis of Released N-Glycans from Cetuximab .............................. 135 Three-Dimensional Cross Correlation (3DCC) of Released N-Glycans ................. from Cetuximab .................................................................................................. 135 6.3 Analysis of Intact mAbs and mAb Sub-Domains ....................................................... 135 MS Analysis of Intact mAbs for N-Glycosylation Analysis ............................... 135 Middle Up Approach for Analyzing the N-Glycosylation of Cetuximab ........... 136 Middle Up Approach for Analyzing the N-Glycosylation of Bevacizumab ....... 137 6.4 Interlaboratory Study on Glycan Analysis .................................................................. 139 MS Analyses of Intact NIST Monoclonal Antibodies ........................................ 139 Middle Up Analyses of NIST Monoclonal Antibodies ...................................... 139 Bottom Up Analyses of NIST Monoclonal Antibodies ...................................... 140 6.5 Histidine-Rich Glycoprotein ....................................................................................... 142 Immobilized Metal Affinity Chromatography by Ni2+-NTA Resin for ................... Isolation of Human Histidine-Rich Glycoprotein ............................................... 143 Size-Exclusion Chromatography of IMAC Enriched Blood Components .............. for Isolation of Human Histidine-Rich Glycoprotein ......................................... 143 SDS-PAGE for Control of HRG Enrichment ..................................................... 143 Dynamic Light Scattering for Determination of Size Distribution of ..................... Enriched HRG .................................................................................................... 144 Acquisition of MALDI Spectra of Intact Histidine-Rich Glycoprotein ............. 144 Plasmin Cleavage of Histidine-Rich Glycoprotein ............................................. 144 6.6 Prolactin-Inducible Protein .......................................................................................... 145 VI OUTLINE Saliva Preparation .............................................................................................. 145 Antibody Affinity Chromatography for Isolation of Salivary PIP ..................... 145 Optimizing Parameters for Isolation of Salivary PIP by AIEX ......................... 146 Comparison of Human PIP from Multiple Saliva Samples by 2D-LC-MS ............ (AIEX-RP) ......................................................................................................... 146 Comparison of Human PIP from Multiple Saliva Samples by 2D-LC-MS ............ (SEC-RP) ............................................................................................................ 147 Combination of AIEX and SEC for PIP Enrichment ......................................... 147 Neuraminidase Digest ........................................................................................ 148 Release of N-Glycans from Human Salivary PIP .............................................. 148 Mass Spectrometric Analyses of PIP Samples ................................................... 148 7 HAZARDS ......................................................................................................................... 150 8 APPENDIX ........................................................................................................................ 152 9 REFERENCES ................................................................................................................... 174 ACKNOWLEDGEMENTS........................................................................................................... 184 DANKSAGUNG ......................................................................................................................... 185 CURRICULUM VITAE .............................................................................................................. 186 AFFIDAVIT ............................................................................................................................... 188 VII ABBREVIATIONS ABBREVIATIONS 1D one-dimensional 3DCC three-dimensional cross correlation aa amino acid ACN acetonitrile ADCC antibody-dependent cellular cytotoxicity AFP α-Fetoprotein AIEX anion exchange chromatography BPC base peak chromatogram CDG congenital disorder of glycosylation CCSD complex carbohydrate structure database CFG Consortium for Functional Glycomics CHO chinese hamster ovary CID collision-induced dissociation COSY correlation spectroscopy CRC colorectal cancer CRD carbohydrate-recognition domain CV column volume DAC diammonium citrate DHAP 2,5-dihydroxyacetophenone DHB 2,5-dihydroxybenzoic acid DLS dynamic light scattering DTT 1,4-D/L-dithiothreitol EDC extracted delta chromatogram EDTA ethylenediaminetetraacetic acid EGF epidermal growth factor EGFR epidermal growth factor receptor EIC extracted ion chromatogram ER endoplasmic reticulum ESI electrospray ionization FA formic acid GBP glycan-binding protein VIII ABBREVIATIONS GCDFP-15 gross cystic disease fluid protein 15 gp17 glycoprotein 17 hc heavy chain HCC hepatocellular cancer HPLC high performance liquid chromatography HR high resolution HRG histidine-rich glycoprotein IAA iodoacetamide IEX
Load more

Recommended publications
  • The Membrane Complement Regulatory Protein CD59 and Its Association with Rheumatoid Arthritis and Systemic Lupus Erythematosus
    Current Medicine Research and Practice 9 (2019) 182e188 Contents lists available at ScienceDirect Current Medicine Research and Practice journal homepage: www.elsevier.com/locate/cmrp Review Article The membrane complement regulatory protein CD59 and its association with rheumatoid arthritis and systemic lupus erythematosus * Nibhriti Das a, Devyani Anand a, Bintili Biswas b, Deepa Kumari c, Monika Gandhi c, a Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India b Department of Zoology, Ramjas College, University of Delhi, India c University School of Biotechnology, Guru Gobind Singh Indraprastha University, India article info abstract Article history: The complement cascade consisting of about 50 soluble and cell surface proteins is activated in auto- Received 8 May 2019 immune inflammatory disorders. This contributes to the pathological manifestations in these diseases. In Accepted 30 July 2019 normal health, the soluble and membrane complement regulatory proteins protect the host against Available online 5 August 2019 complement-mediated self-tissue injury by controlling the extent of complement activation within the desired limits for the host's benefit. CD59 is a membrane complement regulatory protein that inhibits the Keywords: formation of the terminal complement complex or membrane attack complex (C5b6789n) which is CD59 generated on complement activation by any of the three pathways, namely, the classical, alternative, and RA SLE the mannose-binding lectin pathway. Animal experiments and human studies have suggested impor- Pathophysiology tance of membrane complement proteins including CD59 in the pathophysiology of rheumatoid arthritis Disease marker (RA) and systemic lupus erythematosus (SLE). Here is a brief review on CD59 and its distribution, structure, functions, and association with RA and SLE starting with a brief introduction on the com- plement system, its activation, the biological functions, and relations of membrane complement regu- latory proteins, especially CD59, with RA and SLE.
    [Show full text]
  • ABH Secretor and Lewis Subtype Status Peter J
    Metabolic and Immunologic Consequences of ABH Secretor and Lewis Subtype Status Peter J. D’Adamo, ND, and Gregory S. Kelly, ND Abstract Determining ABH secretor phenotype and/or Lewis (Le) blood group status can be useful to the metabolically-oriented clinician. For example, differences in ABH secretor status drastically alter the carbohydrates present in body fluids and secretions; this can have profound influence on microbial attachment and persistence. Lewis typing is one genetic marker which might help identify subpopulations of individuals genetically prone to insulin resistance, autoimmunity, and heart disease. Understanding the clinical significance of ABH secretor status and the Lewis blood groups can provide insight into seemingly unrelated aspects of physiology, including variations in intestinal alkaline phosphatase activity, propensities toward blood clotting, reliability of some tumor markers, the composition of breast milk, and several generalized aspects of the immune function. Since the relevance of ABH blood group antigens as tumor markers and parasitic/bacterial/viral receptors and their association with immunologically important proteins is now well established, the prime biologic role for ABH blood group antigens may well be independent and unrelated to the erythrocyte. (Altern Med Rev 2001;6(4):390-405) Functional and Genetic Factors Involved in ABH Secretion The term “ABH secretor,” as used in blood banking, refers to secretion of ABO blood group antigens in fluids such as saliva, sweat, tears, semen, and serum. A person who is an ABH secretor will secrete antigens according to their blood group; for example, a group O individual will secrete H antigen, a group A individual will secrete A and H antigens, etc.
    [Show full text]
  • Blood Group Have Increased Susceptibility to Symptomatic \(Vibrio\) \(Cholerae\) O1 Infection
    Individuals with Le(a+b−) Blood Group have Increased Susceptibility to Symptomatic \(Vibrio\) \(cholerae\) O1 Infection The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Arifuzzaman, Mohammad, Tanvir Ahmed, Mohammad Arif Rahman, Fahima Chowdhury, Rasheduzzaman Rashu, Ashraful I. Khan, Regina C. LaRocque, et al. 2011. Individuals with Le(a+b−) blood group have increased susceptibility to symptomatic \(Vibrio\) \(cholerae\) O1 infection. PLoS Neglected Tropical Diseases 5(12): e1413. Published Version doi:10.1371/journal.pntd.0001413 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:9369412 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Individuals with Le(a+b2) Blood Group Have Increased Susceptibility to Symptomatic Vibrio cholerae O1 Infection Mohammad Arifuzzaman1,2, Tanvir Ahmed1, Mohammad Arif Rahman1, Fahima Chowdhury1, Rasheduzzaman Rashu1, Ashraful I. Khan1, Regina C. LaRocque2,3, Jason B. Harris2,4, Taufiqur Rahman Bhuiyan1, Edward T. Ryan2,3,5, Stephen B. Calderwood2,3,6., Firdausi Qadri1*. 1 Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B), Dhaka, Bangladesh, 2 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America,
    [Show full text]
  • SPECIFICATION SPN214/4 the Clinical Significance of Blood Group Alloantibodies and the Supply of Blood for Transfusion Copy Numb
    SPECIFICATION SPN214/4 The Clinical Significance of Blood Group Alloantibodies and the Supply of Blood for Transfusion This Specification replaces Copy Number SPN214/3 Effective 03/05/17 Summary of Significant Changes Change of author to Nicole Thornton from Geoff Daniels (retired). Update to blood group systems (new systems added) Update to some rare antibodies due to availability of new data Change of regional coordinators and associated contact information Removal of unnecessary information to improve clarity Purpose This document outlines current knowledge on the clinical significance of blood group alloantibodies. Its prime purpose is to enable clinical decisions to be made regarding the management and blood transfusion support of patients with blood group antibodies that are not commonly encountered and for which antigen-negative blood is not available in the routine stock. The overall aim is to ensure that a uniform RCI Clinical Policy for the supply of blood for transfusion is implemented throughout the NHSBT. Definitions BSH British Committee for Standards in IAT Indirect Antiglobulin Test Haematology IBGRL International Blood Group DHTR Delayed Haemolytic Transfusion Reference Laboratory Reaction IRDP International Rare Donor Panel HDFN Haemolytic Disease of the Fetus NHSBT NHS Blood and Transplant and Newborn NFBB National Frozen Blood Bank HTR Haemolytic Transfusion Reaction RCI Red Cell Immunohaematology Applicable Documents ESD121 Guidelines for pre-transfusion INF1302: HGP project – targets, phenotype compatibility procedures
    [Show full text]
  • Actinomyces Adenosine Diphosphate Adenylate
    Volume 192, Supplement FEBS LETTERS December 1985 ACTINOMYCES The status of Y,, and maintenance energy as biologically in- See: MICROORGANISMS terpretable phenomena Tempest D W & Neijssel 0 M (1984) Annu. Rev. Microbial. 38,459 ADENOSINE DIPHOSPHATE Phosphoenolpyruvate-pyruvate metabolism in bivalve mol- lusts Zwaan A de & Dando P R (1984) Mol. Physiol. 5,285 Involvement of poly(ADP-ribose) in the radtation response of mammalian cells Ben-Hur E (1984) Int. .I. Radiat. Biol. 46,659 ADENYLATE CYCLASE ADP-ribose in DNA repair - a new component of DNA ex- See. ENZYMES AND ENZYME REGULATION cision repair Shall S (1984) Advan. Radmt. Btol. 11, 1 ADIPOSE TISSUE ADENOSINE MONOPHOSPHATE Regulation of adipose tissue lipolysis through reversible phosphorylatton of hormone-sensitive lipase Effects of cyclic adenosine 3’,5’-monophosphate and calcium Belfrage P. Fredrikson G. Olsson H & Stralfors P (1984) on cellular function and growth of mast cells [In Japanese; Advan. Cyclic Nucl. Prot. Phosph. Res. 17, 351 English abstract] Ichikawa A (1984) Yakugaku Zusshi, 104, 1109 Adipose tissue glycogen synthesis [Mmireview] Eichner R D (1984) ht. J. Biochem. 16,257 The role of cyclic AMP m insulin release Malaisse W J & Malaisse-Lagae F (1984) Experientiu, 40, Modulatton of adipose tissue fat composition by diet: a review 1068 Field C J & Clandinin M T (1984) Nutr. Res. 4,743 Multiple roles of ATP in the regulation of sugar transport in muscle and adipose tissue ADENOSINE TRIPHOSPHATE Gould M K (1984) Trends Biochem. Sci. 9, 524-527 Brown adipose tissue thermogenesis: mechanisms of control Electrophysiologic effects of adenosine triphosphate and aden- and relation to energy balance and obesity [Minisymposium] osine on the mammahan heart: clinical and experimental as- Himms-Hagen J & others (1984) Can.
    [Show full text]
  • Blood Group Antigen Lewis B Antibody - with BSA and Azide Mouse Monoclonal Antibody [Clone SPM194 ] Catalog # AH11267
    10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Blood Group Antigen Lewis B Antibody - With BSA and Azide Mouse Monoclonal Antibody [Clone SPM194 ] Catalog # AH11267 Specification Blood Group Antigen Lewis B Antibody - Blood Group Antigen Lewis B Antibody - With With BSA and Azide - Background BSA and Azide - Product Information The Lewis histo-blood group system comprises Application ,2,3, a set of fucosylated glycosphingolipids that are Primary Accession P21217 synthesized by exocrine epithelial cells and Other Accession 2525, 169238 circulate in body fluids. The glycosphingolipids Reactivity Human, Guinea function in embryogenesis, tissue Pig differentiation, tumor metastasis, Host Mouse inflammation, and bacterial adhesion. They are Clonality Monoclonal secondarily absorbed to red blood cells giving Isotype Mouse / IgG1, rise to their Lewis phenotype. This gene is a kappa member of the fucosyltransferase family, Calculated MW 45kDa KDa which catalyzes the addition of fucose to precursor polysaccharides in the last step of Blood Group Antigen Lewis B Antibody - With Lewis antigen biosynthesis. It encodes an BSA and Azide - Additional Information enzyme with alpha(1,3)-fucosyltransferase and alpha(1,4)-fucosyltransferase activities. Lewis Gene ID 2525 blood group antigens are carbohydrate moieties structurally integrated in mucous Other Names secretions. Lewis antigen system alterations Galactoside 3(4)-L-fucosyltransferase, have been described in gastric carcinoma and 2.4.1.65, Blood group Lewis associated lesions. Anomalous expression of alpha-4-fucosyltransferase, Lewis FT, Lewis B antigen has been found in some Fucosyltransferase 3, Fucosyltransferase III, non-secretory gastric carcinomas and FucT-III, FUT3, FT3B, LE colorectal cancers.
    [Show full text]
  • Blood Type Biochemistry and Human Disease By
    Blood Type Biochemistry and Human Disease By: D. Rose Ewald and Susan C.J. Sumner This is the peer reviewed version of the following article: D. Rose Ewald & Susan C.J. Sumner. (2016). Blood Type Biochemistry and Human Disease. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 8(6), 517-535. doi:10.1002/wsbm.1355 which has been published in final form at https://doi.org/10.1002/wsbm.1355. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. ***© 2016 Wiley Periodicals, Inc. Reprinted with permission. No further reproduction is authorized without written permission from Wiley. This version of the document is not the version of record. *** Abstract: Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks.
    [Show full text]
  • Immunohematology
    Immunohematology Journal of Blood Group Serology and Education Celebrating 2 Ye5ars Volume 25, Number 3, 2009 Immunohematology Journal of Blood Group Serology and Education Volume 25, Number 3, 2009 Contents Letter to the Readers 89 Introduction to Vol. 25, No. 3, of Immunohematology J.P. AuBuchon Invited Review: Milestones Series 90 Pioneers of blood group serology in the United States: 1950–1990 S.R. Pierce Review 95 MNS blood group system: a review M.E. Reid Review 102 Quality activities associated with hospital tissue services C.M. Hillberry and A.J. Schlueter Review 107 Logistical aspects of human surgical tissue management in a hospital setting B.M. Alden and A.J. Schlueter Review 112 Lewis blood group system review M.R. Combs Review 119 Recognition and management of antibodies to human platelet antigens in platelet transfusion–refractory patients R.R. Vassallo Review 125 Detection and identification of platelet antibodies and antigens in the clinical laboratory B.R. Curtis and J.G. McFarland Review 136 Investigating the possibility of drug-dependent platelet antibodies J.P. AuBuchon and M.F. Leach 141 Announcements 142 Advertisements 146 Instructions for Authors Editors-in-Chief Managing Editor Sandra Nance, MS, MT(ASCP)SBB Cynthia Flickinger, MT(ASCP)SBB Philadelphia, Pennsylvania Philadelphia, Pennsylvania Connie M. Westhoff, PhD, MT(ASCP)SBB Technical Editors Philadelphia, Pennsylvania Christine Lomas-Francis, MSc New York City, New York Senior Medical Editor Geralyn M. Meny, MD Dawn M. Rumsey, ART(CSMLT) Philadelphia, Pennsylvania Glen Allen, Virginia Associate Medical Editors David Moolten, MD Ralph R. Vassallo, MD Philadelphia, Pennsylvania Philadelphia, Pennsylvania Editorial Board Patricia Arndt, MT(ASCP)SBB Brenda J.
    [Show full text]
  • International – Molecular Pathology Catalog 2020
    Catalog 2020 (International) Doc. No. 937-4096.0 Rev D 2020 Dear Customer, We are pleased to present the BioGenex Molecular Pathology Catalog. As a vertically integrated company, we develop, manufacture and market highly innovative and fully automated systems for cancer diagnosis, prognosis and therapy selection. Xmatrx® systems redefine complete automation for the molecular pathology laboratory and standardize the protocol from baking through final cover-slipping in three simple steps - Load, Click and View. Compared to any other system on the market, Xmatrx® systems offer clean intense stain(s), automate more assay steps, and enable automation of technologies for the future molecular pathology laboratory. • Xmatrx® ELITE integrates All-in-One staining of IHC, ISH, special stains and beyond • Xmatrx® Infinity is a high-performance staining platform for life sciences and translational research • Xmatrx® ULTRA Dx is the next-generation system with new features such as Auto Drain, Auto DAB mixing and with new technologies • Xmatrx® ULTRA Rx is the next-generation system with new features and technologies for life sciences and translation research • NanoMtrx® 300 is a fully-automated, 30-slide benchtop compact system with micro-chamber® for IHC and ISH • NanoMtrx® 100 is a fully-automated, 10-slide benchtop compact system with micro-chamber® for IHC and ISH • NanoVIP® is a ten-slide automated system specifically designed for FISH • Xmatrx® MINI enables in situ PCR and nucleic acid hybridization with tools for building micro-chamber We also offer a series of i6000TM systems with very high throughput: 200 slides in an 8-hour shift. To maintain our tradition of offering superior solutions for the emerging needs of your laboratory, we offer a broad range of molecular pathology products for IHC, ISH, miRNA, multiplex and special staining of tissues including 400+ primary antibodies, molecular probes, detection systems, and ancillaries.
    [Show full text]
  • Do Blood Group Antigens and the Red Cell Membrane Influence Human
    cells Review Do Blood Group Antigens and the Red Cell Membrane Influence Human Immunodeficiency Virus Infection? Glenda M. Davison 1,2,* , Heather L. Hendrickse 1 and Tandi E. Matsha 1 1 SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7530, South Africa; [email protected] (H.L.H.); [email protected] (T.E.M.) 2 Division of Haematology, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa * Correspondence: [email protected]; Tel.: +27-21-959-6562; Fax: +27-21-959-6760 Received: 26 January 2020; Accepted: 26 March 2020; Published: 31 March 2020 Abstract: The expression of blood group antigens varies across human populations and geographical regions due to natural selection and the influence of environment factors and disease. The red cell membrane is host to numerous surface antigens which are able to influence susceptibility to disease, by acting as receptors for pathogens, or by influencing the immune response. Investigations have shown that Human Immunodeficiency Virus (HIV) can bind and gain entry into erythrocytes, and therefore it is hypothesized that blood groups could play a role in this process. The ABO blood group has been well studied. However, its role in HIV susceptibility remains controversial, while other blood group antigens, and the secretor status of individuals, have been implicated. The Duffy antigen is a chemokine receptor that is important in the inflammatory response. Those who lack this antigen, and type as Duffy null, could therefore be susceptible to HIV infection, especially if associated with neutropenia.
    [Show full text]
  • Clinical Significance of Antibodies to Antigens in the ABO, MNS, P1PK, Rh, Lutheran, Kell, Lewis, Duffy, Kidd, Diego, Yt, and Xg Blood Group Systems
    R EVIEW Proceedings from the International Society of Blood Transfusion Working Party on Immunohaematology, Workshop on the Clinical Significance of Red Blood Cell Alloantibodies, September 9, 2016, Dubai Clinical significance of antibodies to antigens in the ABO, MNS, P1PK, Rh, Lutheran, Kell, Lewis, Duffy, Kidd, Diego, Yt, and Xg blood group systems N.M. Thornton and S.P. Grimsley This report is part of a series reporting the proceedings from the ABO Blood Group System International Society of Blood Transfusion (ISBT) Working Party on Immunohaematology Workshop on the Clinical Significance The ABO blood group system was the first to be of Red Blood Cell Alloantibodies. The aim of the workshop was to review information regarding the clinical significance discovered and is still the most clinically important. Despite of alloantibodies to red blood cell antigens recognized by the consisting of just four polymorphic antigens—A, B, A,B, and ISBT. The first 12 systems will be covered in this report. A1—the genetics and carbohydrate chemistry underpinning It is understandable that many of the most clinically important 6 antibodies are directed toward antigens found in the blood the expression of these antigens is complex. Because these group systems discovered earlier in history. The ABO system was antigens are abundant on RBCs and because most adults have the first to be discovered and remains the most clinically “naturally occurring” antibodies to the antigens that they lack, important regarding transfusion. Immunohematology 2019; ABO antibodies are clinically significant; anti-A, -B, and -A,B 35:95–101. cause severe intravascular hemolytic transfusion reactions Key Words: clinical significance, red blood cell alloantibodies, (HTRs).
    [Show full text]
  • Distribution of Clinically Relevant Erythrocyte Antigens Among Blood
    ORIGINAL ARTICLE UDK 613.2:612.118(497.6 RS) Gordana Guzijan1, Janja Bojanić2, Dragica Jojić3, Distribution of Clinically Relevant Biljana Jukić1, Sandra Mitrović1, Erythrocyte Antigens among Blood Veselka Ćejić1 1 Institute for Transfusion Medicine Donors of the Republic of Srpska of the Republic of Srpska, Banja Luka, BiH 2 The Public Health Institute, the Republic of Srpska, Banja Luka, BiH 3 The Paediatric Clinic, University Hospital Clinical Centre Banja Luka ABSTRACT Introduction: Identifying voluntary blood donors with rare phenotype characteristics Contact address: is the basic precondition for creating a registry of blood donors with rare blood Gordana Guzijan Jovana Jančića 3 groups. 78000 Banja Luka, BiH E-mail: [email protected] Aims of the study: Determining the presence of phenotypes in the clinically most Telephone: +387 65 829 649 relevant blood group systems in regular blood donors at the Institute for Transfusion Medicine of the Republic of Srpska, with the goal to create a national registry of blood donors with rare blood groups. Patients and Methods: Determination of antigens in the Rh system was performed by the automatic microplate method, as well as by gel method. Determination of antigens in other blood group systems Kell, Kidd, Duffy, MNS, Lewis and Lutheran was performed by the gel method and test tube method. Altogether 384 blood donors were screened between 2012 and 2013. Results: The analysis of Rh phenotypes showed that most of the examinees had the Rh phenotype CcDee ,29.7% and 26.0% the ccddee, and the least of them had the Rh phenotype ccddEe 0.8%, Ccddee 1.6% and ccDee 2.3%.
    [Show full text]