Blood Groups
15.1.1 Blood Groups
Blood groups are characterized by erythrocyte (red blood cell) antigens with common immunologic properties (eg, group A). Blood group systems are series of such antigens encoded by a single gene or by a cluster of 2 or 3 closely linked homologous genes1-3 (eg, ABO system).
There are about 600 recognized erythrocyte antigens.2 The International Society of Blood Transfusion (ISBT) designates around 270 blood group antigens. Of these, around 250 belong to 1 of 29 systems.3,4 (Other antigens remain in officially designated series or collections.) Some antigens are erythrocyte-specific; others appear widely, but specifically, on cells of other organs and tissues.
The discovery of blood group antigens was prompted by hemolytic disease of the newborn and transfusion reactions, but many antigens have since been implicated in infection and other disease processes1,5; whether fundamentally or incidentally is not known.6 Erythrocytes are estimated to contain millions of antigen sites.1
Traditional/Popular Nomenclature.7-10
Traditional blood group system nomenclature is typically used in medical publications. It comprises several approaches, and, therefore, sometimes the same entity (eg, a particular erythrocyte antigen) can be expressed by more than 1 term. Editors generally should follow author preference.
The principal elements named are blood group systems, antigens, phenotypes, genes, and alleles.
Blood Group Systems.
The following list shows the blood group system names and symbols. (The column of derivations of names of blood group systems is provided for background interest1,2,9,11-14 [also Geoff Daniels, PhD, written communications, May 13 and 17, 2004].)
System Name |
Symbol |
Derivation |
|---|---|---|
ABO |
ABO |
Alphabetical (A and B); letter O may derive from “ohne” (German for without) |
Chido/Rogers |
Ch/Rg |
Names of antibody makers |
Colton |
Co |
Name of antibody maker |
Cromer |
Cromer |
Name of antibody maker |
Diego |
Di |
Name of antibody maker |
Dombrock |
Do |
Name of antibody maker |
Duffy |
Fy |
Name of antibody maker |
Gerbich |
Ge |
Name of antibody maker |
Gill |
GIL |
Name of antibody maker |
Globoside |
GLOB |
Globoside synthetase |
Hh |
H |
Concept (“heterogenetic”) |
I |
I |
Concept (“individuality”) |
Indian |
In |
Geographic |
John Milton Hagen |
JMH |
Name of antibody maker |
Kell |
K |
Name of antibody maker (Kelleher) |
Kidd |
Jk |
Initials of infant child of antibody maker (K already in use) |
Knops |
Kn |
Name of antibody maker |
Kx |
Kx |
Association with Kell and X chromosome |
Lewis |
Le |
Name of antibody maker |
Lutheran |
Lu |
Name of antibody maker (actually Lutteran9 or Luteran13) |
LW or Landsteiner/Wiener |
LW |
Names of investigators |
MNSs |
MNS |
M, N: the word immune; S: location (Sydney, Australia) |
U (an antigen of the MNSs system): universal |
||
Ok |
OK |
Family name initials (Kobutso; letters reversed because “Ko” was in use) |
P |
P |
Alphabetical |
Raph |
Raph |
Name of antibody maker |
Rh |
Rh |
Rhesus monkeys (antigens were LW antigens) |
Scianna |
Sc |
Name of antibody maker |
Xg |
Xg |
X chromosome and location (Grand Rapids, Michigan) |
Yt or Cartwright |
Yt |
… |
The ISBT prefers an all-capital style for blood group system symbols3 (see “ISBT Name and Number” in this section).
The following are examples of usage:
ABO incompatibility
A cell
type AB recipient
type O donor
Hemolytic disease of the newborn primarily occurs from incompatibilities of the Rh, ABO, or Kell blood groups.
Antigens.
Antigen terms use single or dual letters, often with a qualifier that is a letter (usually superscript) or number (subscript or typeset on the line).
A, A1, A2, Ax, B
Cra
Fya, Fyb
He
Jka, Jkb
K, k
Kpa, Kpb, Ku, Jsa, Jsb
K11, K12, K13, K14, Km
Lea, Leb, LebH, ALeb, BLeb
Lua, Lub
Lu3, Lu4, Lu5, Lu6
P1
Sc1, Sc2
Xga
The Rh system historically has used 3 alternative schemes: the Rh-Hr nomenclature, the CDE nomenclature, and the numerical nomenclature.7 Terms from the first, eg, rh′, hr″, rhx, RhA, are appropriate in historical discussions, but otherwise, the CDE and numerical nomenclatures are favored:
D, C, E, c, e, f
Ce, Cw, Cx… BARC
or
Rh1, Rh2, Rh3, Rh4, Rh5, RH6
RH7, RH8, RH9… RH52
The following are examples of antigen-term usage:
anti-Jka alloantibody
Rh(D) incompatibility
human monoclonal anti-D antibodies
Studies using anti-Ch and anti-Rg antisera have demonstrated Ch and Rg determinants on complement component C4.
Phenotypes.
In phenotypic expressions—terms that describe an individual’s blood group or type—the presence or absence of an antigen is often indicated by a plus or minus sign:
Antigen: M
Phenotype: M+
M+N+S−s+ erythrocytes
M+N+S−s+ phenotype
Lowercase letters that were superscripts in the antigen terms are set on the line in parentheses in phenotypic terms.
Antigen: Lub
Phenotype: Lu(b+)
More than 98% of the Western population is Lu(b+).
If the numerical terminology is used for the antigen, a colon is added in the phenotype.
Antigen: Sc1
Phenotype: Sc:1
the Sc:1,−2,3 phenotype
Other sample phenotypic terms include the following:
Fy(a−b+), Fy(a+b−), Fy(a−b−)
Jk(a−b+), Jk(a+b−), Jk(a+b+)
K+k−, Kp(a−b+), Js(a−b+)
Le(a−b+), Le(a+b−), Le(a−b−)
Lu(a−b+), Lu(a+b−), Lu(a+b+)
M+N+, M+, N−, M−N+, S+s+, S+s−, S−s+
P1, P2, P1k, P2k
Xg(a+), Xg(a−)
the silent phenotype Le(a−b−)
A superscript w can indicate a weak reaction:
M+w
K+w
Fy(a+w)
The ABO system is an exception: its phenotypic terms do not feature plus or minus signs; A (not A+) indicates A erythrocyte antigens; O (not A− B−) indicates the absence of A and B antigens:
Groups: O, A, B, AB, Oh, OhA
Subgroups: A1, A2, A1B, A2B
OhA individuals do not express the H determinant but do have the A allele.
Terms for Rh phenotypes, which do not feature plus and minus signs, are also in use:
D-positive (Rh positive)
D-negative (Rh negative)
DccE, DCce
RH:1,2,3
Rhnull
Absence of C, c, E, and/or e antigens is indicated with 1 or 2 minus signs14:
Dc−
D− −
Usage note: Terms such as O+ (“O positive”), A+, and AB− are common parlance as shorthand for blood of the ABO system and its Rh specificity. However, in scientific articles, use standard terms that specifically indicate Rh status:
O Rh-positive
O Rh+
or more specific designations of phenotype:
group B, D-negative
group A, Rh D-positive
In a blood group profile, elements from different systems may be separated by commas, as above, or, for more complex specificities, with semicolons:
The patient’s blood was group B, Rh positive, D+ C+ c+ E− e+; M+ N+ S− s+; P1+; Le(a−b−); K− k+; Fy(a−b+); Jk(a+b−).15(p846)
Note that in phenotypic expressions commas do not appear within elements of the same blood group system:
D+ C+ c+ E− e+
Not: D+, C+, c+, E−, e+
Commas may be dispensed with between different blood group systems in brief expressions:
K+Fy(a+)
Genes.
As with International Standard Gene Nomenclature (the “HUGO” recommendations; see 15.6.2, Genetics, Human Gene Nomenclature), ISBT gene terms are italicized. Traditional blood-group gene symbols often mixed uppercase and lowercase. However, symbols recommended by ISBT, like those of HUGO, use all capital letters.
The following list3,4,9,16 shows gene symbols associated with blood group systems.
Traditional |
ISBT |
HUGO |
|---|---|---|
ABO |
ABO |
ABO |
Ch/Rg |
C4A, C4B |
C4A, C4B |
Co |
AQP1 |
AQP1(was CO) |
Cromer |
DAF |
CD55 (was DAF) |
Di |
SLC4A1 |
SLC4A1 |
Do |
DO |
ART4 (was DO) |
Fy |
FY |
DARC (was FY) |
Ge |
GYPC |
GYPC |
[GIL] |
AQP3 |
AQP3 |
[Globoside] |
B3GALT3 |
B3GALT3 |
Hh |
FUT1 |
FUT1 |
[I] |
GCNT2 |
GCNT2 |
In |
CD44 |
CD44 |
Jk |
SLC14A1 |
SLC14A1 |
[JMH] |
SEMA7A |
SEMA7A |
K |
KEL |
KEL |
Kn |
CR1 |
CR1 |
Kx |
XK |
XK |
Le |
FUT3 |
FUT3 |
Lu |
LU |
BCAM (was LU) |
LW |
ICAM4 |
ICAM4 |
MN or MNSs |
GYPA, GYPB, GYPE |
GYPA, GYPB, GYPE |
Ok |
BSG |
BSG (previously OK, CD147) |
P1 |
P1 |
A4GALT |
Raph |
CD151 (was MER2) |
CD151 |
Rh |
RHCE, RHD |
RHCE, RHD |
Sc |
ERMAP |
SC |
Xg |
XG, MIC2 |
XG |
Yt |
ACHE |
ACHE |
Gene symbols expressed according to ISBT4 or HUGO16 are preferred to traditional symbols.
Parenthetic synonyms are helpful:
BSG(formerly OK)
ERMAP(also called SC)
The Lutheran inhibitor gene is expressed as follows:
In(Lu) [traditional]
INLU [standard]
Do not confuse In with the traditional Indian blood group gene symbol, In (recommended gene symbol: CD44).
Alleles.
The italicized blood group symbol—ABO, MNS, RH, etc—is used for alleles (which are also distinguished by an asterisk and number). In the following example, compare the gene symbol and an allele term from the same blood group:
SC*1 [allele]
ERMAP [gene symbol]
Note that qualifiers that are subscripts in antigen terms are superscripts in allelic terms, eg, A1 antigen, A1 allele). The following are examples of genotypic terms.
A1O, A1A1, A1B, OO
MN, MM, NN, MSNs
DCe/DCe (R1R1)
DcE/dce (R2r)
dce/dce (rr)
D− −/D− −
LuaLua, LubLub, LuaLub
Lele, LeLe, lele
FyaFya, FybFyb, FyFy
Kk, KpaKpb, JsbJsb
JkaJka, JkbJkb, JkaJkb
XgaXga, XgaXg, XgXg
XgaY, XgY
For expressing alleles, the ISBT gives an option, eg, either Fya or FY*1 (with appropriate superscripts and italics). Mixing the 2 styles, however (eg, FY*A), is not appropriate (Geoff Daniels, PhD, written communications, May 13 and 17, 2004).
ISBT Name and Number.3,7,17,18
In the 1980s the Working Party on Terminology for Red Cell Surface Antigens of the ISBT developed an alphanumeric system of blood group notation, intended to provide “a uniform nomenclature that is both eye and machine readable and in keeping with the genetic basis of blood groups.”7(p273) The system does not replace traditional terminology; rather, its terms correspond to traditional terms. It is also used to assign new terms as needed. In the ISBT terminology, each blood group system has a symbol, usually of 1 to 3 capital letters, and a system number of 3 digits.
System |
Antigen No. Within System | |||||
|---|---|---|---|---|---|---|
Name |
Symbol |
No. |
001 |
002 |
003 |
004 |
ABO |
ABO |
001 |
A |
B |
A,B |
A1 |
MNS |
MNS |
002 |
M |
N |
S |
s |
Rh |
RH |
004 |
D |
C |
E |
c |
Kx |
XK |
019 |
kx |
|||
AB
ABO:1,2,3
001:1,2,3
The following are acceptable terms for the antigen A,B:
A,B
ABO3
001003
Authors may use ISBT terms in parentheses following traditional terms:
AB (1.3)
D (RH1)
Lea(007001)
The patient’s red blood cells were negative for Cromer blood system antigens Cra (CROM1) and Tca (CROM2).
In notations that use plus and minus signs to express presence and absence of particular antigens, phenotypic expressions in the numerical notation use a colon and numbers in place of letters, as in these examples:
LE:−1,2 [for Le(a−b+)]
FY:1,−2 [for FY(a+b−)]
Genotypic expressions are italicized:
FY 1/2 or FY*1/2 (for FyaFyb)
Tables of blood group systems, symbols, antigens, and ISBT numbers are available at the ISBT Committee on Terminology for Red Cell Surface Antigens website.4