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Studies of the ABO and FORS Histo-Blood Group Systems: Focus on Flow Cytometric and Genetic Analysis Studies of the ABO and FORS Histo-Blood Group Systems: Focus on Flow Cytometric and Genetic Analysis Hult, Annika 2013 Link to publication Citation for published version (APA): Hult, A. (2013). Studies of the ABO and FORS Histo-Blood Group Systems: Focus on Flow Cytometric and Genetic Analysis. Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University. Total number of authors: 1 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Studies of the ABO and FORS histo-blood group systems: Focus on flow cytometric and genetic analysis Doctoral thesis by Annika K Hult Division of Hematology and Transfusion Medicine Department of Laboratory Medicine Lund University With the approval of the Lund University Faculty of Medicine, this thesis will be defended on May 24, 2013 at 09:15 in Segerfalksalen, BMC, Lund Faculty opponent: Dr. Fumi-ichiro Yamamoto Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC) Badalona, Spain 203 Studies of the ABO and FORS histo-blood group systems: Focus on flow cytometric and genetic analysis Annika K Hult Copyright © Annika K Hult Lund University, Faculty of Medicine, Laboratory Medicine Doctoral Dissertations Series 2013:63 ISBN 978-91-87449-33-8 ISSN 1652-8220 Printed in Sweden by Media-Tryck, Lund University Lund 2013 En del av Förpacknings- och Tidningsinsamlingen (FTI) Till mormor och morfar “ 'Cause people often talk about being scared of change but for me I'm more afraid of things staying the same 'cause the game is never won by standing in any one place for too long” From Jesus of the moon by Nick Cave Table of Content ABBREVIATIONS ....................................................................................................... 6 LIST OF PAPERS ........................................................................................................ 8 BACKGROUND......................................................................................................... 10 Blood groups ..................................................................................................................... 10 Historical perspective .................................................................................................. 10 Terminology .................................................................................................................. 11 Antigens and antibodies .............................................................................................. 12 Structure and function ................................................................................................ 14 Orphan and emerging antigens .................................................................................. 17 Disease associations .................................................................................................... 18 Glycosyltransferases ........................................................................................................ 21 Glycosylation ................................................................................................................ 21 Structure and function ................................................................................................ 22 The glycosyltransferase gene family 6 ....................................................................... 24 THE ABO BLOOD GROUP SYSTEM .............................................................. 27 ABO antigens .................................................................................................................... 27 Normal expression ....................................................................................................... 27 Modification of ABO expression ................................................................................ 29 ABO Biochemistry ............................................................................................................ 30 Biosynthesis and tissue distribution ......................................................................... 30 A1 versus A2 ................................................................................................................... 34 The ABO gene ................................................................................................................... 35 The gene ....................................................................................................................... 35 Common alleles ........................................................................................................... 35 Gene regulation ........................................................................................................... 38 The gene product ......................................................................................................... 40 Weak expression of ABO ................................................................................................ 43 Allelic enhancement .................................................................................................... 44 Weak expression due to unknown factors ............................................................... 45 Typing discrepancies with normal ABO expression ............................................... 45 Weak ABO expression due to weak/no expression of H antigen .......................... 46 Weak ABO alleles ............................................................................................................. 47 A3 alleles ....................................................................................................................... 47 Ax alleles ....................................................................................................................... 48 Afinn and Abantu alleles .................................................................................................. 49 Ael alleles ....................................................................................................................... 49 CisAB and B(A) alleles ................................................................................................ 49 Bweak alleles ................................................................................................................... 51 Hybrid alleles ............................................................................................................... 52 THE FORS BLOOD GROUP SYSTEM ........................................................... 53 Species and tissue distribution .................................................................................. 53 Expression in malignancies ....................................................................................... 54 GBGT1, the Forssman gene ........................................................................................ 54 Forssman negativity in humans ................................................................................ 55 Pathogen interaction................................................................................................... 56 PRESENT INVESTIGATIONS ........................................................................... 57 Aims for this thesis .......................................................................................................... 57 Methodological considerations ...................................................................................... 58 Flow Cytometry and ABO ........................................................................................... 58 Paper I ............................................................................................................................... 60 Investigation into A antigen expression on O2 heterozygous group O-labeled red blood cell units Paper II .............................................................................................................................. 62 Many genetically defined ABO subgroups exhibit characteristic flow cytometric patterns Paper III ............................................................................................................................. 64 Weak A Phenotypes Associated with Novel ABO Alleles Carrying the A2-related 1061C Deletion and Various Missense Amino Acid Substitutions Paper IV ............................................................................................................................. 66 Flow cytometry evaluation of red blood cells mimicking naturally occurring ABO subgroups after modification with variable amounts of function-spacer-lipid A and B constructs Paper
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