The Blood Group Antigen FactsBook
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About this ebook
- Highly Commended 2013 BMA Medical Book Award for Internal Medicine
- Includes more than 330 entries on blood group antigens in individual factsheets
- Offers a logical and concise catalogue structure for each antigen in an improved interior design for quick reference
- Written by three international experts from the field of immunohematology and transfusion medicine
Read more from Marion E. Reid
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The Blood Group Antigen FactsBook - Marion E. Reid
syndrome).
SECTION I
The Introductory Chapters
1 Introduction
2 Organization of the data
1
Introduction
Aims of this FactsBook
The purpose of this FactsBook is to provide key information relating to the erythrocyte membrane components carrying blood group antigens, the genes encoding them, the molecular basis of the antigens and phenotypes, characteristics, and the clinical significance of blood group antibodies. Only key references are given to allow the interested reader to obtain more details. The book is designed to be a convenient, easy-to-use reference for those involved in the field of transfusion medicine, as well as medical technologists, students, physicians, and researchers interested in erythrocyte blood group antigens.
This FactsBook contains information about the blood group antigens that have been numbered by the International Society of Blood Transfusion Working Party on Red Cell Immunogenetics and Blood Group Terminology¹–⁴. The blood group systems and the antigens within each system are listed by their traditional name, and are arranged in the same order as described by the ISBT Working Party for Red Cell Immunogenetics and Blood Group Terminology. See Table 1.1 for an overview of the blood group systems. Those antigens not in a blood group system are accommodated in Collections (200 series), in the 700 Series of Low-Incidence Antigens or in the 901 Series of High-Incidence Antigens (for latest ISBT terminology, see www.isbt-web.org).
Table 1.1 Blood group systems with gene name and chromosome location
^For up to date HUGO gene names see http://www.genenames.org/
Selection of entries
Blood group antigens are surface markers on the outside of the red blood cell (RBC) membrane. They are proteins and carbohydrates attached to lipid or protein. A model for the types of membrane components carrying blood group antigens is shown in Figure 1.1. A blood group antigen is defined serologically by antibodies made by a human, and in order to be assigned a number by the ISBT Working Party the antigen must be shown to be inherited. Historically, antigens associated with forms of polyagglutination have not been numbered by the ISBT; however, in Section III we have included a table summarizing the characteristics of T, Tn, Tk, and Cad.
Figure 1.1 Model of RBC membrane components that carry blood group antigens.Not shown is the Ch/Rg blood group system. Ch/Rg antigens are carried on C4d, which is adsorbed from plasma onto RBC membrane components.
Terminology
The nomenclature used for erythrocyte blood group antigens is inconsistent. While several antigens were named after the proband whose RBCs carried the antigen or who made the first known antibody, others were assigned an alphabetical or a numerical notation. Even within the same blood group system, antigens have been named using different schemes, and this has resulted in a cumbersome terminology for describing phenotypes. The ISBT Working Party established a system of upper case letters and numbers to represent blood group systems and blood group antigens in a format that will allow both infinite expansion and computer-based storage. These symbols and numbers are designed for use in computer databases (no lower case letters) and are short (for column headings). A comprehensive review of terminology and its recommended usage can be found in Garratty, et al.⁵.
Throughout this book, the systems and antigens are named by the traditional name, but we also give the ISBT symbol, the ISBT number, and obsolete names that have been used in the literature. We have included a brief description of how the blood group systems and antigens were named.
The following are examples of how to write antigens, antibodies, phenotypes, and genotypes.
In addition to the ISBT terminology for antigens and traditional allele names, the ISBT Working Party recently agreed on a proposed terminology for blood group alleles⁴. Since the introduction of a new naming system for thousands of alleles is a complicated and cumbersome procedure, it is anticipated that certain changes to the new terminology are unavoidable. Despite this, we have used the currently agreed nomenclature to familiarize the reader with the new allele names. However, we encourage the use of the official and constantly updated lists of allele names found at www.isbt-web.org. These allele names are restricted to those with a phenotypic effect and intended for use in Transfusion Medicine. Their use does not require sequencing of the entire allele. The rules for naming alleles and for obtaining a number for a new allele may be found at www.isbt-web.org.
References
1. Daniels GL, et al. Blood group terminology 1995 ISBT working party on terminology for red cell surface antigens. Vox Sang. 1995;69:265–279.
2. Daniels GL, et al. Blood group terminology 2004. Vox Sang. 2004;87:316.
3. Daniels G, et al. International Society of Blood Transfusion committee on terminology for red cell surface antigens: Cape Town report. Vox Sang. 2007;92:250–253.
4. Storry JR, et al. International Society of Blood Transfusion working party on red cell immunogenetics and blood group terminology: Berlin report. Vox Sang. 2011;101:77–82.
5. Garratty G, et al. Terminology for blood group antigens and genes: Historical origins and guidelines in the new millennium. Transfusion. 2000;40:477–489.
2
Organization of the data
Section II is organized into four main parts: (i) the blood group systems; (ii) the blood group collections; (iii) the 700 Series of Low-Incidence Antigens; and (iv) the 901 Series of High-Incidence Antigens. For the systems, facts pertaining to the gene, carrier molecule, and antigens, and the clinical relevance of antibodies are given. For the collections, series of low-incidence antigens, and series of high-incidence antigens, facts pertaining to the antigens and antibodies are given. All are listed in ISBT numerical order. The format for the facts sheets displaying the data about the systems and the antigens is explained below; that for the collections and high-incidence antigens is similar. The 700 Series of Low-Incidence Antigens are given in a table. Section III consists of facts in lists and tables where the information encompasses more than one antigen or blood group system. Other related information is also included. We will use prevalence
throughout this book, because it is the word used to describe a permanent/inherited characteristic on the phenotypic level.
ISBT Blood Group Systems
Both the ISBT system symbol and traditional name are used in the section headings. Information is provided under the following headings.
Number of Antigens
The total number of antigens in the system is indicated. The antigens are listed under the headings: polymorphic
(in blue font); high prevalence (in red font); and low prevalence (in green font). Table 2.1A lists the blood group systems and antigens currently recognized by the ISBT Working Party for Red Cell Immunogenetics and Blood Group Terminology. If a number assigned to an antigen becomes inappropriate, the number becomes obsolete and is not reused; such antigens are noted with three small dots (…).
Table 2.1A Blood group antigens assigned to each system
… = Obsolete numbers. For the obsolete antigens see www.isbt-web.org.
Terminology
Both the traditional name and the ISBT symbol for the blood group system are given as headers. Under this subheading, the ISBT symbol, ISBT number (parenthetically)¹–⁴, other, obsolete, names that have been associated with the system, the CD number (if any), and a brief description of how the system was named are given.
Expression
This section relates to the component on which the antigens in a blood group system are carried. Several blood group antigens occur naturally in soluble form in body fluids (e.g., saliva, urine, plasma). If a naturally occurring soluble form of the carbohydrate antigen or carrier protein is available, it will be indicated in this section. Soluble forms of an antigen can be used for inhibition tests to confirm or eliminate antibody activity. If the soluble form of the antigen is to be used for inhibition studies, the substance must be obtained from a person who inherited the antigen of interest and be made isotonic. An ideal negative dilution control for this test would be the particular fluid from a person who did not inherit the antigen of interest⁵. A soluble form of many antigens can be produced through recombinant technology.
Some of the components carrying blood group antigens have been detected on other blood cells and tissues by use of various methods, including testing with polyclonal and monoclonal antibodies or by Northern blot analysis. However, it cannot be assumed that detection of the carrier molecule equates with the expression of the RBC antigen(s).
Under the subheading Other blood cells,
we refer to cells in the peripheral blood excluding RBCs because it goes without saying that RBCs express all the components carrying blood groups (except in null phenotypes).
Table 2.1B Blood group antigens assigned to each system: extension 1
Table 2.1C Blood group antigens assigned to each system: extension 2
Gene
The chromosomal location for the genes encoding proteins associated with blood group systems is taken from original papers and reviews of the chromosome assignments⁶ and how blood groups were cloned⁷. The chromosome number, arm [short p (upper on diagrams); long q (lower on diagrams)], and band number are given. The name of the gene used is that recommended by the ISBT, with alternative names in parenthesis. If the presence of a blood group antigen is detected by serological means, the gene is named by the corresponding ISBT system symbol, an asterisk followed by the antigen number, in italics to indicate the specific allele, e.g., FY*01 for the allele encoding Fya. The organization of the gene in terms of number of exons, kilobase pairs of gDNA, and an overview map are provided. The gene product name (and alternatives) is given.
Database accession numbers
Key GenBank accession numbers and the Entrez gene number are given. The Blood Group Antigen Gene Mutation Database (http://www.ncbi.nlm.nih.gov/gv/rbc/xslcgi.fcgi?cmd=bgmut/home or enter dbRBC
in a search engine) is a useful website which gives information about alleles relevant to blood groups and hyperlinks to other websites and original articles.
Molecular bases of antigens and phenotypes
Tables listing alleles encoding blood group variants, together with relevant information, are given. The alleles and their names are those assigned by the ISBT Working Party as of December 2011. For updates, go to the ISBT website (www.isbt-web.org). The accession number for the reference allele is indicated, and key nucleotide differences are noted for each allele. Cases where the nucleotide substitution introduces or ablates a restriction enzyme site (indicated, respectively, by +
or –
) are documented. A blank indicates that, despite our best efforts, the information could not be ascertained and not, necessarily, that there is no change. The approximate prevalence of the allele in different ethnicities are noted using the following general terms: many = 13 or more examples; several = 6 to 12 examples; few = 2 to 5; and rare = 1. Amino acid changes (using the three-letter code; see Table 2.2) are also given for each variant. In line with the ISBT allele nomenclature, silent nucleotide changes are not given unless there is an effect on antigen expression. For each protein-based blood group system, the reference allele encodes all high prevalence antigens in that system. The protein encoded by a variant allele will differ by the unique expression, or absence, of an antigen. The variant protein will express all high-prevalence antigens of that blood group system, except for the specific variant antigen, e.g., the protein encoded by KEL*02.06 lacks Jsb, expresses the antithetical antigen Jsa, and also all other Kell high-prevalence antigens, k, Kpb, Ku, K11, etc.
Table 2.2 Blood group antigens in the collections
Obsolete Collections: 201 (GE), 202 (CROMER), 203 (IN), 204 (AU), 206 (GY), and 211 (WR). For obsolete antigens see www.isbt-web.org.
^= M and N antigens associated with different sialic acid-carrying oligosaccharides on GPA.
Table 2.3 Series of low-prevalence and high-prevalence antigens
For obsolete antigens see www.isbt-web.org.
The molecular bases for each antigen are also given on the individual antigen pages. Other tables list alleles encoding so-called mod (greatly reduced antigen expression that may require adsorption/elution for detection) or null phenotypes. If the allelic backbone of the altered allele is known, this is noted, e.g., CO*01N.03 and CO*01N.04 means that the silencing nucleotide change(s) is on a Co(a+) background. If the background was not reported, the allele is written, e.g., CO*N.01 and CO*N.02. Compound heterozygosity
means two different alleles encoding a weak phenotype, one allele encoding a weak phenotype and one allele encoding a null phenotype or two different null