Human Blood Groups

Geoff Daniels

• Editore: Wiley-Blackwell
• Anno: 2013
• ISBN:
  9781118493540
• Edizione: 3
• Argomento: Medicine
• Categoria: Hematology

Human Blood Groups is a comprehensive and fully referenced text covering both the scientific and clinical aspects of red cell surface antigens, including: serology, inheritance, biochemistry, molecular genetics, biological functions and clinical significance in transfusion medicine.

Since the last edition, seven new blood group systems and over 60 new blood group antigens have been identified. All of the genes representing those systems have now been cloned and sequenced.

This essential new information has made the launch of a third edition of Human Blood Groups, now in four colour, particularly timely.

This book continues to be an essential reference source for all those who require clinical information on blood groups and antibodies in transfusion medicine and blood banking.

1

Human Blood Groups: Introduction

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1.1 Introduction

1.2 Blood group terminology

1.3 Chromosomal location of blood group genes

1.4 DNA analysis for blood group testing

1.5 Structures and functions of blood group antigens

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1.1 Introduction

What is the definition of a blood group? Taken literally, any variation or polymorphism detected in the blood could be considered a blood group. However, the term blood group is usually restricted to blood cell surface antigens and generally to red cell surface antigens. This book focuses on the inherited variations in human red cell membrane proteins, glycoproteins, and glycolipids. These variations are detected by alloantibodies, which occur either ‘naturally’, due to immunisation by ubiquitous antigens present in the environment, or as a result of alloimmunisation by human red cells, usually introduced by blood transfusion or pregnancy. Although it is possible to detect polymorphism in red cell surface proteins by other methods such as DNA sequence analysis, such variants cannot be called blood groups unless they are defined by an antibody.

Blood groups were discovered at the beginning of the twentieth century when Landsteiner [1,2] noticed that plasma from some individuals agglutinated the red cells from others. For the next 45 years, only those antibod­ies that directly agglutinate red cells could be studied. With the development of the antiglobulin test by Coombs, Mourant, and Race [3,4] in 1945, non-agglutinating antibodies could be detected and the science of blood group serology blossomed. There are now 339 authenticated blood group antigens, 297 of which fall into one of 33 blood group systems, genetically discrete groups of antigens controlled by a single gene or cluster of two or three closely linked homologous genes (Table 1.1).

Table 1.1 Blood group systems.

Most blood group antigens are synthesised by the red cell, but the antigens of the Lewis and Chido/Rodgers systems are adsorbed onto the red cell membrane from the plasma. Some blood group antigens are detected only on red cells; others are found throughout the body and are often called histo-blood group antigens.

Biochemical analysis of blood group antigens has shown that they fall into two main types:

1 protein determinants, which represent the primary products of blood group systems; and

2 carbohydrate determinants on glycoproteins and glycolipids, in which the products of the genes controlling antigen expression are glycosyltransferase enzymes.

Some antigens are defined by the amino acid sequence of a glycoprotein, but are dependent on the presence of carbohydrate for their recognition serologically. In this book the three-letter code for amino acids is mainly used, though the single-letter code is often employed in long sequences and in some figures. The code is provided in Table 1.2.

Table 1.2 The 20 common amino acids: one- and three-letter codes.

A	Ala	Alanine
C	Cys	Cysteine
D	Asp	Aspartic acid
E	Glu	Glutamic acid
F	Phe	Phenylalanine
G	Gly	Glycine
H	His	Histidine
I	Ile	Isoleucine
K	Lys	Lysine
L	Leu	Leucine
M	Met	Methionine
N	Asn	Asparagine
P	Pro	Proline
Q	Gln	Glutamine
R	Arg	Arginine
S	Ser	Serine
T	Thr	Threonine
V	Val	Valine
W	Trp	Tryptophan
Y	Tyr	Tyrosine

In recent years, molecular genetical techniques have been introduced into the study of human blood groups and now most of the genes governing blood group systems have been cloned and sequenced (Table 1.1). Many serological complexities of blood groups are now explained at the gene level by a variety of mechanisms, including point mutation, unequal crossing-over, gene conversion, and alternative RNA splicing.

Discovery of the ABO blood groups first made blood transfusion feasible and disclosure of the Rh antigens led to the understanding, and subsequent prevention, of haemolytic disease of the fetus and newborn (HDFN). Although ABO and Rh are the most important systems in transfusion medicine, many other blood group antibodies are capable of causing a haemolytic transfusion reaction (HTR) or HDFN. Red cell groups have been important tools in forensic science, although this role was diminished with the introduction of HLA testing and has recently been displaced by DNA ‘fingerprinting’. For many years blood groups were the best human genetic markers and played a major part in the mapping of the human genome.

Blood groups still have much to teach us. Because red cells are readily available and haemagglutination tests relatively easy to perform, the structure and genetics of the red cell membrane proteins and lipids are understood in great detail. With the unravelling of the complexities of blood group systems by molecular genetical techniques, much has been learnt about the mechanisms responsible for the diversification of protein structures and the nature of the human immune response to proteins of different shapes resulting from variations in amino acid sequence.

1.2 Blood Group Terminology

The problem of providing a logical and universally agreed nomenclature has dogged blood group serologists almost since the discovery of the ABO system. Before going any further, it is important to understand how blood groups are named and how they are categorised into systems, collections, and series.

1.2.1 An Internationally Agreed Nomenclature

The International Society of Blood Transfusion (ISBT) Working Party on Red Cell Immunogenetics and Blood Group Terminology was set up in 1980 to establish a uniform nomenclature that is ‘both eye and machine readable’. Part of the brief of the Working Party was to produce a nomenclature ‘in keeping with the genetic basis of blood groups’ and so a terminology based primarily around the blood group systems was devised. First the systems and the antigens they contained were numbered, then the high and low frequency antigens received numbers, and then, in 1988, collections were introduced. Numbers are never recycled: when a number is no longer appropriate it becomes obsolete.

Blood group antigens are categorised into 33 systems, seven collections, and two series. The Working Party produced a monograph in 2004 to describe the terminology [5], which was most recently updated in 2011 [6]. Details can also be found on the ISBT web site [7].

1.2.2 Antigen, Phenotype, Gene and Genotype Symbols

Every authenticated blood group antigen is given a six-digit identification number. The first three digits represent the system (001 to 033), collection (205 to 213), or series (700 for low frequency, 901 for high frequency); the second three digits identify the antigen. For example, the Lutheran system is system 005 and Lu^a, the first antigen in that system, has the number 005001. Each system also has an alphabetical symbol: that for Lutheran is LU. So Lu^a is also LU001 or, because redundant sinistral zeros may be discarded, LU1. For phenotypes, the system symbol is followed by a colon and then by a list of antigens present, each separated by a comma. If an antigen is known to be absent, its number is preceded by a minus sign. For example, Lu(a−b+) becomes LU:−1,2.

Devising a modern terminology for blood group alleles is more complex. One antigen, the absence of an antigen, or the weakness or absence of all antigens of a system may be encoded by several or many alleles. Over the last few years the Working Party has been developing a new terminology for bloods group alleles. Unfortunately at the time of publication of this book, it was still incomplete, controversial, and in draft form. Consequently, it has only partially been used in this book. Basically, alleles have the system symbol followed by an asterisk followed in turn by a number or series of numbers, separated by full stops, representing the encoded antigen and the allele number. Alternatively, in some cases a letter can be used instead of a number. For example, Lu^a allele can be LU*01 or LU*A. Genotypes have the symbol followed by an asterisk followed by the two alleles separated by a stroke. For example, Lu^a/Lu^b becomes LU*01/02 or LU*A/B. The letters N and M represent null and mod. For example, one of the inactive Lu^b alleles responsible for a null phenotype is LU*02N.01, the 02 representing the Lu^b allele, even though no Lu^b antigen is expressed. Genes, alleles, and genotypes are italicised. For lists of blood group alleles in the ISBT and other terminologies see the ISBT and dbRBC web sites [7,8].

Symbols...