Characteristics of Blood Group Antibodies

Immunoglobulin In vitro characteristics Associated with Antigen Frequency (%) Remarks

class
May
ISBT Saline Papain Complement
Antibody IgM IgG IAT show HDFN HTR Caucasians Blacks Others
Symbol RT 37ºC* binding
dosage
ABO (ISBT No 001) & H Blood Group (ISBT No 018) Systems
Asians: 28
Yes for IgM Yes for IgG Yes
Anti-A ABO1 Yes Yes hh   No to moderate No to severe 43 27 Mexicans: 28
component component some hemolytic
South American Indians: 0
Asians: 27
Yes for IgM Yes for IgG Yes
Anti-B ABO2 Yes Yes hh   No to moderate No to severe 9 20 Mexicans: 13
component component some hemolytic
South American Indians: 0
Yes for IgM Yes for IgG Asians: 57 Anti-A,B is only produced by group O individuals, and cannot be separated
Anti-A,B ABO3 Yes Yes hh   Rare No to severe None to mild/delayed 56 51
component component Mexicans: 45 into anti-A and anti-B.

Frequency: 1-2% in blood group A2, 25% in blood group A2B, 99% in
Anti-A1 ABO4 Yes Rare Yes Rare hh   Rare No None to mild/delayed 34 19 Asians: 27
blood group Ax.

Possible in Oh No to severe in Alloanti-H is present in the serum of Bombay (Oh) and Para-Bombay (H+w)
Anti-H H1 Yes Rare Yes Rare hh   Some All populations: 99.9
mothers Oh and H+w people. O cells show the strongest antigen expression, A1B cells the weakest.

MNS (ISBT No 002) Blood Group System

IgM No (except in No (except in Many examples are naturally-occurring. May be pH dependant.
Anti-M MNS1 Yes Yes Rare ii Yes 78 74  
and IgG extremely rare cases) extremely rare cases) More common in children, and in patients with bacterial infections.
IgM Many examples are naturally-occurring. Rare N-S-s-U- individuals make an
Anti-N MNS2 Yes Yes Rare ii Yes   No No 72 75  
and IgG antibody that reacts with N on GPA and GPB, and is usually clinically significant.

Anti-S MNS3 Some Most Some Most V Yes Some No to severe (rare) No to moderate (rare) 55 31   The S antigen is sensitive to trace amounts of chlorine.

Reacts often by IAT after incubation at RT or lower.

Anti-s MNS4 Yes Yes Some Most V Yes Rare No to severe (rare) No to mild (rare) 89 93  
A pH of 6.0 enhances the reactivity of some anti-s.

Anti-U MNS5 Yes No Yes   Mild to severe Mild to severe 99.9 99   Autoantibody has been identified to cause WAIHA in rare cases.

P1PK (ISBT No 003) & GLOB (ISBT No 028) Blood Group Systems
There is considerable variation in the strength of P1 expression on RBC’s.
No to moderate/ Cambodian,
Anti-P1 P1PK1 Yes Rare Yes Very rare hh   Rare No 79 94 This variation is inherited, and at least partially dependent on the zygosity
delayed (rare) Vietnamese: 20
of P1 alleles.
No to mild
Yes Autoanti-P exists as a biphasic autohemolysin in PCH, detected by the Donath-
Anti-P GLOB1 Yes Yes Some Some hh   (in Pk mothers with No to severe (rare) All populations: > 99.9
some hemolytic Landsteiner test may occur after viral illness, particularly in children.
anti-P)
Anti-PP1Pk Alloantibody in sera of p- people may cause complete hemolysis in fresh serum
  Yes Some Some hh   Yes Yes Yes 100  
(Tja) Anti-PP1Pk is a potential cause of early abortion.

Rh (ISBT No 004) Blood Group System 

Mild to severe/ Asians: 99

Anti-D RH1 Some Most Rare Yes hh Extremely rare Mild to severe 85 92 Occurs frequently with anti-C.
immediate or delayed Native Americans: 99

Mild to severe/
Anti-C RH2 Yes Yes Rare Yes hh Yes No Mild 68 27 Asians: 93 Anti-C is often found in antibody mixtures, especially with anti-G or anti-D.
immediate or delayed

Mild to severe/
Anti-E RH3 Yes Yes Some Yes hh Yes No Mild 29 22 Asians: 39 Occurs frequently with anti-c.
immediate or delayed

Mild to severe/
Anti-c RH4 Some Most Rare Yes hh Yes No Mild to severe 80 98 Asians: 47 Occurs frequently with anti-E.
immediate or delayed
Mild to moderate/
Anti-e RH5 Some Most Rare Yes hh Yes No Rare, usually mild delayed/ 98 Asians: 96 Occurs frequently with anti-C.
hemoglobinuria
Mild to severe/ Finns: 4
Anti-Cw RH8 Yes Yes Yes Yes hh   No Mild to moderate 2 1 Most Cw+ are C+; rare examples are C-.
immediate or delayed Latvians: 9

Lutheran (ISBT No 005) Blood Group System

Characteristic reaction picture of “loose” agglutinates surrounded by
Anti-Lua LU1 Yes Yes Most Some to i Rare No to mild (rare) No 8 5   unagglutinated RBCs in tube technique. Sera containing anti-Lua often also
contain HLA antibodies.

Anti-Lub LU2 Yes Yes Some Most to i Rare Mild Mild to moderate All populations: 99.8

Anti-Lu3 is only made by immunized individuals of the rare recessive type

Anti-Lu3 LU3 Yes No Yes Rare No data No data All populations: 100
Lu(a-b-).
Kell (ISBT No 006) Blood Group System
Asians: rare Anti-K may not react well by LISS procedures. Some bacteria trigger
Mild to severe/
Anti-K KEL1 Some Most Some Yes   Rare Mild to severe (rare) 9 2 Iranian Jews: 12 production of IgM anti-K. Expression of K can be acquired through
delayed/hemolytic
Arabs: 25 bacterial activity in vivo and in vitro.
Mild to moderate/
Anti-k KEL2 Rare Most Rare Yes   No Mild to severe (rare) 99.8 100  
delayed

Mild to moderate/ In the presence of Kpa, other inherited Kell antigens are suppressed (cis-mo-
Anti-Kpa KEL3 Yes Very rare Yes   No Mild to severe 2 < 0.01  
delayed difying effect) to varying degrees. Anti-Kpa appears often combined with anti-K.

No to moderate/
Anti-Kpb KEL4 Rare Yes Rare Yes   No Mild to moderate 100  Sera containing anti-Kpb often contain anti-K.
delayed

No to moderate/
Anti-Jsa KEL6 Rare Most Rare Yes to h   No Mild to severe < 0.01 20  
delayed

Mild to moderate/
Anti-Jsb KEL7 Yes Very rare Yes to h   No Mild to severe 100 99  
delayed

Lewis (ISBT No 007) Blood Group System

No
Yes No Anti-Lea and anti-Leb in conjunction are frequently naturally occurring antibodies
Anti-Lea LE1 Most Some Yes Some hh   (rare cases of 22 23  
some hemolytic (one mild case) made by Le(a-b-) people, especially during pregnancy.
hemolytic reactions)
There are two kinds of anti-Leb: anti-LebH (LE4), reacting with group O and A2
Yes Le(b+) RBCs, and anti-LebL, reacting with all Le(b+) RBCs. Other antibodies
Anti-Leb LE2 Most Some Yes Some hh   No No 72 55  
some hemolytic react specifically with the compund antigens, e.g., ALeb (LE5) and BLeb (LE6).

Duffy (ISBT No 008) Blood Group System 

Mild to severe (rare)/ Asians: 99
Anti-Fya FY1  Rare Yes Very rare Yes ii Some Rare Mild to severe (rare) 66 10
immediate/delayed Thais: 97
Mild to severe (rare)/ Chinese: 9.2
Anti-Fyb FY2 Very rare Yes Very rare Yes ii Some Rare Mild (rare) immediate (rare)/ 83 23 Asians: 18.5  
delayed Thais: 31
Asians: 99.9
Mild to moderate/
Yemeni Jews: 99
Anti-Fy3 FY3 Yes   Yes Yes Rare Mild (rare) immediate (rare)/ 100 32  
Israeli Jews: 96
delayed/hemolytic
Israeli Arabs: 75
Kidd (ISBT No 009) Blood Group System 
Yes Yes Yes if IgM No to severe/
Mild to
Anti-Jka JK1 many many Rare Yes h present immediate or delayed/ 77 92 Asians: 72 Anti-Jka deteriorates in vitro and in vivo.
Some moderate (rare)
IgG + IgM IgG + IgM some hemolytic hemolytic
Yes Yes Yes if IgM No to severe/
Anti-Jkb JK2 many many Rare Yes h Some present No to mild (rare) immediate or delayed/ 74 49 Asians: 76 Anti-Jkb deteriorates in vitro and in vivo.
IgG + IgM IgG + IgM some hemolytic hemolytic
Yes No to severe/ Polynesians,
Anti-Jk3 JK3 Rare Yes Rare Yes h   No to mild 100  
some hemolytic immediate or delayed Finns: > 99

Diego (ISBT No 010) Blood Group System

Most populations: 0.01
Yes South American Indians: from 2 in Caracas Indians to 54
No to severe/
Anti-Di a
DI1 (often IgG1 Yes   Some Mild to severe in Kainganges Indians,
delayed
and IgG3) Japanese: 12, Chippewa Indians (Canada): 11, Chinese: 5,
Hispanics: 1, Poles: 0.47

No to moderate/ Most populations: 100

Anti-Dib DI2 Yes Yes Yes No Mild  
delayed Native Americans: 99
No to severe/ Alloanti-Wra is often a naturally-occurring antibody and is found in the serum
Anti-Wra DI3 Yes Yes Yes Yes     Mild to severe immediate or delayed/ All populations: < 0.01 of 1-2% of blood donors. It is frequently found in multispecific sera and is a
hemolytic common specificity in patients with AIHA.
Yt (ISBT No 011) Blood Group System 
Yes
No to moderate (rare)/ Most populations: > 99.8 Experts agree that anti-Yta are often benign and antigen-negative blood
Anti-Yta YT1 (some are Yes V   Some No
delayed Israeli Jews: 98.6, Israeli Arabs: 97.6, Israeli Druse: 97.4 may not need to be transfused.
IgG4)
Europeans: 8, Israeli Jews: 21.3,
Anti-Ytb YT2 Yes Yes V   No No Israeli Arabs: 23.5, Israeli Druse: 26 Anti-Ytb is rare and usually occurs in sera with other antibodies.
Not found in Japanese
Xg (ISBT No 012) Blood Group System

Anti-Xga XG1 Rare Most Some Most ii   Some No No 89 Females, 66 Males 

Dombrock (ISBT No 014) Blood Group System

Positive DAT but no Delayed and acute/ Japanese: 24
Anti-Doa DO1   Yes Yes h     67 55 Anti-Doa is notorious for disappearing in vivo.
clinical HDFN hemolytic Thais: 14
Positive DAT but no
Anti-Dob DO2 Yes Yes h Acute and delayed 82 89    
clinical HDFN
Colton (ISBT No 015) Blood Group System
No to moderate/
Anti-Coa CO1 Very rare Yes   Yes   Some Mild to severe (rare) delayed/immediate/ All populations: 99.5  
hemolytic
No to moderate/
Anti-Cob CO2 Yes   Yes   Rare Mild All populations: 10
delayed/hemolytic
Chido/Rodgers (ISBT No 017) Blood Group System
Most anti-Ch1 are IgG2 and IgG4. A few reports describe anaphylactic
Yes
transfusion reactions from plasma products and platelets. Soluble plasma
Anti-Ch1 CH/RG1 (mostly IgG2 Yes i     No Not hemolytic Most populations: 96 Japanese: 99
antigen in donor blood may neutralise patient’s antibody. Anti-Ch1 reacts
and IgG4)
strongly with C4-coated RBCs.
A few reports describe anaphylactic transfusion reactions from plasma
Anti-Rg1 CH/RG11 Yes Yes i     No Not hemolytic All populations: > 98
products and platelets.
Knops (ISBT No 022) Blood Group System

Anti-Kna KN1 Yes Yes i     No No 94.5 99.9    

Anti-McCa KN3 Yes Yes i   No No 98 94  

Anti-Yka KN5 Yes Most i   No No 92 98  

John Milton Hagen, JMH (ISBT No 026) Blood Group System

JMH- or JMH-weak phenotypes can be (transiently) acquired;
Anti-JMH JMH1 Yes Yes i     No No All populations: 100
anti-JMH in that case is mostly IgG4.
I (ISBT No 027) Blood Group System & Ii (ISBT No 207) Blood Group Collection
Most common cold autoantibody, rare alloantibody in i-adults,
Yes
Anti-I I1 Yes Rare Yes Very rare hh   No No Adults: > 99 high titre at 0-4°C, wide thermal range, associated with CHAD
some hemolytic
and Mycoplasma pneumoniae infection.

Yes Autoantibody can occur in serum of people with infectious mononucleosis

Anti-i I2 Yes Rare Most Very rare hh   Rare No 100  
some hemolytic and some lymphoproliferative disorders.

JR (ISBT No 032) Blood Group System

Positive DAT but usually The Jr(a-) phenotype has been found mostly in Japanese and other Asians,
Anti-Jra JR1 Some Yes Yes h Some no HDFN; however one Probably All populations: > 99 but also in persons of northern European extraction, Beduin Arabs,
fatal case of HFDN and in one Mexican.

Lan (ISBT No 033) Blood Group System

No to severe/ Lan - found in about 1 in 20,000 people; found in Blacks,
Anti-Lan LAN1 Yes Yes Some No to mild All populations: > 99
hemolytic Caucasians and Japanese.
Vel (ISBT No 034) Blood Group System
Yes Yes
Red cells with a weak Vel expression may be mistyped as Vel-.
(usually a (usually a Yes Positive DAT No to severe/
Anti-Vel VEL1 Yes hh   All populations: > 99.9 Vel- RBCs have been found in 1 in ~4,000 people and 1 in ~1,700 in
mixture of mixture of some hemolytic to severe hemolytic
Norwegians and Swedes.
IgM and IgG) IgM and IgG)
Cost (ISBT No 205) Blood Group Collection
Most
Anti-Csa COST1 Yes Yes No No 95  
populations: > 98

Anti-Csb COST2 Yes Yes Most populations: 34 Only one example of antibody is published.

Bibliography Legend* Abbreviations

■ 
Reid M E, Lomas-Francis C, Olsson M L. THE BLOOD GROUP ANTIGEN FactsBook. 3rd ed. Papain treated cells, 37ºC AIHA Autoimmune
Oxford: Elsevier; 2012 hh markedly enhanced CHAD Cold hemagglutinin disease
■ 
Daniels G. Human Blood Groups. 3rd ed. Oxford: Wiley-Blackwell; 2013 h enhanced F Female
unaffected HDFN Hemolytic disease of the fetus and newborn
■ 
Klein H G, Anstee D. Mollinson’s Blood Transfusion in Clinical Medicine. 12th ed. Oxford: HTR Hemolytic transfusion reaction
Wiley-Blackwell; 2014 i weakened
IAT Indirect antiglobulin test
i i denatured
■ Issitt P D, Anstee D. Applied Blood Group Serology. 4th ed. Durham (NC): Montgomery V variable
Ig Immunoglobulin
Scientific Publications; 1998 ISBT International Society of Blood Transfusion
LISS Low-ionic strength solution
M Male
PCH Paroxysmal cold hemoglobinuria
RBC Red blood cell
RT Room temperature

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