Classifications in Blood Group Terminology

Introduction

The red cell membrane contains many anchored surface proteins; many of these are polymorphic and carry the different blood groups. Most blood group antigens are glycoproteins and their specificity is mostly determined either by the oligosaccharide or amino acid sequence. The 30 human blood group system genes have been identified and sequenced and all the polymorphisms are now known. Most blood group polymorphisms result from single nucleotide polymorphisms (SNPs) encoding amino acid substitutions in either a glycosyltransferase or extracellular domain of a red cell membrane protein.

All authenticated antigens fall into one of four classifications: systems, collections, low and high incidence antigens:

  • Systems consist of one or more antigens controlled at a single gene locus, or by two or more very closely linked homologous genes with little or no observable recombination between them.
  • Collections (200 series) consist of serologically, biochemically, or genetically related antigens, which do not fit the criteria required for system status.
  • 700 Series or low incidence antigens with an incidence of less than 1% and cannot be included in a system or collection.
  • 901 Series or high incidence antigens with an incidence of greater than 90% and cannot be included in a system or collection. 

Terminology Explained

Since their discovery in 1900, a variety of different styles of terminology has been used to denote human blood groups. In 1980 the ISBT established therefore a Working Party (later to become a Committee) to devise and maintain a genetically based numerical terminology for red cell surface antigens. By definition, these antigens must be defined serologically by the use of a specific antibody. All antigens receiving ISBT numbers must have been shown to be inherited characters. The information presented here is an update of one of our publications.

Antigens, phenotypes, genes and genotypes 
  • Each antigen belonging to a blood group system is identified by a 6-digit number. The first 3 digits represent the system (e.g. 006 for Kell), the second 3 the specificity (e.g. 006003 for Kpa). Alternatively, the system symbol followed by the antigen number may be used (e.g. KEL003 or, more usually, KEL3 as sinistral zeros may be removed).
  • Phenotypes are represented by the system symbol, followed by a colon, followed by a list of antigens separated by commas. Those antigens shown to be absent are preceded by a minus sign (e.g. KEL:-1,2,3,4).
  • Alleles are designated by the system symbol, followed by an asterisk, and antigen number, all italicised (e.g. KEL*02). · Genotypes have the system symbol, followed by an asterisk, alleles or haplotypes separated by a slash, all italicised (e.g. KEL*02.03/02). Refer to the allele terminology guidelines and tables for more detail.
  • For collections, antigen, phenotype, gene, and genotype designations are constructed in the same way.
  • For the 700 and 901 series, 700 or 901 replaces the system symbol.
User-friendly and 'everyday' terminology

The numerical terminology was devised primarily for computer storage of information on blood group antigens and to provide a framework for a genetic classification. The numerical terminology is not suitable for everyday communication and many scientists working in the field of human blood groups prefer not to use it in publications. This has led to a variety of alternative names being used for some blood group antigens. In an attempt to introduce some uniformity, a recommended list of alternative names for antigens is provided (see table). In most cases the name or symbol is identical to that originally published, but in a few cases the more commonly used name is provided. In addition, there are recommended formats for describing phenotypes in the alternative terminology.

Criteria Used

Criteria for the establishment of new blood group systems

For an antigen to form a new blood group system:

  • the antigen must be defined by a human alloantibody
  • the antigen must be an inherited character
  • the gene encoding it must have been identified and sequenced
  • its chromosomal location must be known
  • the gene must be different from, and not a closely-linked homologue of, all other genes encoding antigens of existing blood group systems.
Criteria for the inclusion of a new specificity in an established system

All antigens awarded an ISBT number must have been shown to be inherited and at least one of the following four criteria must be met:

  1. An antithetical relationship between a new antigen and one already assigned to the system.
  2. Demonstration that expression of the antigen is associated with a variation in the nucleotide sequence of the gene controlling the system.
  3. Evidence, from a linkage analysis of family data, that the controlling allele is probably a newly recognised form of the pertinent gene, and supporting serological or biochemical information.
  4. Demonstration that an antigen is located on a protein or glycoprotein that carries other antigens belonging to the system. It must be remembered, however, that this could result from post-translational modification of a gene product, such as glycosylation, which would not support inclusion within the system.

 

Criteria for establishment of a blood group collection

A collection must contain two or more antigens that are related serologically, biochemically, or genetically, but which do not fit the criteria required for system status.

 

Criteria for inclusion in the 700 series 
  1. Incidence of <1% in most populations tested.
  2. Distinction from all other numbered low incidence antigens of the 700 series as well as those of the blood group systems and collections.
  3. Demonstration of inheritance through at least 2 generations.

 

Criteria for inclusion in the 901 series
  1. Incidence of >90% in most populations tested.
  2. Distinction from all other numbered high incidence specificities.
  3. Demonstration that the antigen is lacking from the red cells of at least 2 siblings, i.e. that the negative phenotype is genetically determined.

 

Obsolete Numbers

Once a number has been allocated to a specificity, that number cannot be subsequently used for any other specificity. Consequently, if the number of a specificity becomes inappropriate, then that number becomes obsolete. The obsolete numbers are listed here.

ISBT Numerical Designations

Procurement of ISBT Numerical Designations

Symbols for designations of new specificities will consist of 3-6 on-line capital letters and must not duplicate, alphabetically or phonetically, any current or obsolete symbols shown in the tables. Also, symbols used in related fields, such as those used for platelet and leucocyte antigens, must be avoided. Symbols for specificities that may herald new blood group systems, and thus new genes, have the further constraint that they must differ from any symbols given to genes by the HUGO Nomenclature Committee

 

Procedures for acquisition of an ISBT number

The initial stipulation is that materials for defining the new specificity be available for either circulation or in-house testing. Proposals should be submitted with supporting data to the members of the Committee listed below, who are authorised to allocate provisional numbers. All decisions must be ratified by the Committee before being finalised. To submit a proposal for the acquisition of an ISBT number, please contact the following Committee members:

For a specificity number within an established system, see the following contact persons in the table below.

Contact Persons Assigned to Each System

System #

Name Blood Group System 

Responsible Committee Member

001 ABO Martin Olsson
002 MNS Jill Storry
003 P1PK Asa Hellberg
004 RHD Qing Chen
004 RHCE Connie Westhoff
005 LU Christoph Gassner
006 KEL Barbera Veldhuisen
007 Lewis Nick Gleadall
008 FY Nuria Nogues
009 JK Greg Denomme
010 DI Silvano Wendel
011 YT Vered Yahalom
012 XG Jill Storry
013 SC Bill Flegel
014 DO Lilian Castilho
015 CO Franz Wagner
016 LW Christine Lomas Francis
017 Ch/Rg Yanli Ji
018 H Franz Wagner
019 XK Catherine Hyland
020 GE Peter Ligthart
021 CROM Christine Lomas Francis
022 KN Margaret Keller
023 IN Yoshihiko Tani
024 OK Yoshihiko Tani
025 RAPH Vered Yahalom
026 JMH Christoph Gassner
027 I Nicole Thornton
028 GLOB Asa Hellberg
029 GIL Peter Ligthart
030 RHAG Jill Storry
031 FORS Martin Olsson
032 JR Thierry Peyrard
033 LAN Thierry Peyrard
034 Vel Jill Storry
035 CD59 Christoph Weinstock
036 AUG Thierry Peyrard
037 KANNO Yoshihiko Tani
038 SID Åsa Hellberg
039 CTL2 Thierry Peyrard
040 PEL Thierry Peyrard
041 MAM Nicole Thornton
042 EMM William Joseph Lane
043 ABCC1 Thierry Peyrard
Transcription Factors GATA1, KLF1 Margaret Keller 

Blood Group Allele Terminology

As DNA testing for the prediction of blood group phenotypes has become more widely applied, it is important to have an agreed terminology for the multitude of alleles encoding blood group phenotypes. A subgroup of this WP has taken this on and made a decision that two nomenclatures are required:

  1. A comprehensive database in which all blood group alleles can be identified. This would provide the official allele name and would require that the whole coding region of the gene has been sequenced. This is still to be developed.
  2. A transfusion medicine-friendly terminology that can be used when only part of the gene has been sequenced or analysed, such as a single nucleotide polymorphism (SNP).

A draft of general guidelines for 'transfusion medicine' terminology was developed by a group consisting of Geoff Daniels, Marion Reid, Jill Storry, Connie Westhoff, and Martin Olsson.

Additionally, special guidelines for naming RH alleles were developed in parallel by Connie Westhoff, due to the complexity of RH. These two guidelines were approved by the WP, at the Berlin Congress in 2010. Since the terminology was new and took some time to adopt into routine practice, all comments were discussed in 2012. Currently guidelines and tables for 41 of the 43 blood groups are listed, as well mutations in GATA1 and KLF1 responsible for blood group phenotypes. Other systems will be added as they are completed.

Information regarding new alleles should be sent to the blood group-responsible committee member on the front page.

Blood Group Allele Tables

ISBT number

Blood Group System

001 ABO
002 MNS 
003 P1PK
004 RHD
004 RHCE
005 LU 
006 KEL 
007 LE
008 FY
009 JK 
010 DI
011 YT
012 XG
013 SC
014 DO 
015 CO
016 LW
017 CH/RG
018 H
019 XK
020 GE
021 CROM
022 KN
023 IN
024 OK
025 RAPH
026 JMH
027 I
028 GLOB
029 GIL
030 RHAG
031 FORS
032 JR
033 LAN
034 VEL
035 CD59
036 AUG
037 KANNO
038 SID
039 CTL2
040 PEL
041 MAM
042 EMM
043 ABCC1
Transcription Factor GATA1
Transcription Factor KLF1