The term human blood group systems is defined by the International Society of Blood Transfusion (ISBT) as systems in the human species where cell-surface antigens—in particular, those on blood cells—are "controlled at a single gene locus or by two or more very closely linked homologous genes with little or no observable recombination between them",[1] and include the common ABO and Rh (Rhesus) antigen systems, as well as many others; 44 human systems are identified as of December 2022[update].[2]
ISBT No.[3] | System name | System symbol | Structure / function | Chromosome | Antigens | Notes |
---|---|---|---|---|---|---|
001 | ABO | ABO | Carbohydrate (N-Acetylgalactosamine, galactose). | 9q34.2 | A, B, H | Mainly elicit IgM antibody reactions, although anti-H is very rare, see the Hh antigen system (Bombay phenotype, ISBT #18). |
002 | MNS | MNS | GPA / GPB (glycophorins A and B). | 4q31.21 | M, N, S, s | |
003 | P1PK | P | Glycolipid | 22q13.2 | P1, P, and Pk | |
004 | Rh | RH | Protein and glucose. | 1p36.11 | C, c, D, E, e | There is no "d" antigen; lowercase "d" indicates the absence of D. |
005 | Lutheran | LU | Protein (member of the immunoglobulin superfamily). | 19q13.32 | 21 antigens | |
006 | Kell | KEL | Glycoprotein. | 7q34 | K, k, Kpa, Kpb, Jsa and Jsb [4] | |
007 | Lewis | LE | Carbohydrate (fucose residue). | 19p13.3 | Mainly Lea and Leb | Associated with tissue ABH antigen secretion. |
008 | Duffy | FY | Protein (chemokine receptor). | 1q23.2 | Mainly Fya and Fyb | Individuals lacking Duffy antigens altogether are immune to malaria caused by Plasmodium vivax and Plasmodium knowlesi. |
009 | Kidd | JK | Protein (urea transporter). | 18q12.3 | Jka and Jkb | |
010 | Diego | DI | Glycoprotein (band 3, AE 1, or anion exchange). | 17q21.31 | Positive blood is found only among East Asians and Native Americans. | |
011 | Yt | YT | Protein (AChE, acetylcholinesterase). | 7q22.1 | ||
012 | XG | XG | Glycoprotein. | Xp22.33 | ||
013 | Scianna | SC | Glycoprotein. | 1p34.2 | ||
014 | Dombrock | DO | Glycoprotein (fixed to cell membrane by GPI, or glycosyl-phosphatidyl-inositol). | 12p12.3 | ||
015 | Colton | CO | Aquaporin 1. | 7p14.3 | Mainly Co(a) and Co(b) | |
016 | Landsteiner-Wiener | LW | Protein (member of the immunoglobulin superfamily). | 19p13.2 | ||
017 | Chido/Rodgers | CH | C4A C4B (complement fractions). | 6p21.3 | ||
018 | Hh | H | Carbohydrate (fucose residue). | 19q13.33 | ||
019 | XK | XK | Glycoprotein. | Xp21.1 | ||
020 | Gerbich | GE | GPC / GPD (Glycophorins C and D). | 2q14.3 | ||
021 | Cromer | CROM | Glycoprotein (DAF or CD55, regulates complement fractions C3 and C5, attached to the membrane by GPI). | 1q32.2 | ||
022 | Knops | KN | Glycoprotein (CR1 or CD35, immune complex receptor). | 1q32.2 | ||
023 | Indian | IN | Glycoprotein (CD44 adhesion function?). | 11p13 | ||
024 | Ok | OK | Glycoprotein (CD147). | 19p13.3 | ||
025 | Raph | RAPH | Transmembrane glycoprotein. | 11p15.5 | ||
026 | JMH | JMH | Protein (fixed to cell membrane by GPI). Also known as Semaphorin 7A or CD108. | 15q24.1 | ||
027 | Ii | I | Branched (I) / unbranched (i) polysaccharide. | 6p24.2 | ||
028 | Globoside | GLOB | Glycolipid. Antigen P. | 3q26.1 | ||
029 | GIL | GIL | Aquaporin 3.[citation needed] | 9p13.3 | ||
030 | Rh-associated glycoprotein | RHAg | Rh-associated glycoprotein.[citation needed] | 6p21-qter | ||
031 | Forssman | FORS | Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).[citation needed] | 9q34.13 | ||
032 | Langereis[5] | LAN | ABCB6, human ATP-binding cassette (ABC) transporter, mitochondrial porphyrin transporter.[5] | 2q36 | ||
033 | Junior | JR | ABCG2. Multi-drug transporter protein.[citation needed] | 4q22 | ||
034 | Vel | Vel | Human red cell antigens.[citation needed] | 1p36.32 | ||
035 | CD59 | CD59 | — | 11p13 | ||
036 | Augustine | AUG | Protein (transporter).[6] | 6p21.1 | ||
037 | KANNO[7][8] | PRNP | — | 20p13 | ||
038 | SID | SID | 17q21.32 | |||
039 | CTL2 | CTL2 | 19p13.2 | |||
040 | PEL | PEL | 13q32.1 | |||
041 | MAM | MAM | 19q13.33 | |||
042 | EMM | EMM | 4p16.3 | |||
043 | ABCC1 | ABCC1 | 16p13.11 | |||
044 | Er[9] | Er | Protein | Era, Erb, Er3, Er4, and Er5 | Illustrates potential antigenicity of low abundance membrane proteins and contributes to understanding of in vivo characteristics of the Piezo1 protein in transfusion biology |
Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems:[10]
ABO | Rh | Kell | Duffy | Kidd | Lutheran | MNS | Lewis | P | Ii | |
---|---|---|---|---|---|---|---|---|---|---|
Most common in immediate hemolytic transfusion reactions | A | Yes | Fya | Jka | ||||||
Most common in delayed hemolytic transfusion reactions | E,D,C | Jka | ||||||||
Most common in hemolytic disease of the newborn | Yes | D,C | Yes | |||||||
Commonly produce intravascular hemolysis | Yes | Yes | Yes | |||||||
Reactive at room temperature | Yes | M,N | Lea, Leb | P1 | ||||||
Nearly always clinically insignificant | Yes | M,N | Yes | P1 | ||||||
Naturally occurring | Yes | Yes | M,N | Yes | Yes | Yes | ||||
Enhanced by ficain[11] and papain[12] | Yes | Yes | Yes | Yes | P1 | Yes | ||||
Destroyed by ficain[11] and papain[12] | Fya, Fyb | Yes | Yes | |||||||
Displaying dosage | Cc, Ee | Yes | Yes | Yes |
Blood compatibility testing is performed before blood transfusion, including matching of the ABO blood group system and the Rh blood group system, as well as screening for recipient antibodies against other human blood group systems. Blood compatibility testing is also routinely performed on pregnant women and on the cord blood from newborn babies, because incompatibility puts the baby at risk for developing hemolytic disease of the newborn.[13][14] It is also used before hematopoietic stem cell transplantation, as it may be responsible for some cases of acute graft-versus-host disease.[15]
Other human blood group systems than ABO and Rh have a relatively small risk of complications when blood is mixed.[16] Therefore, in emergencies such as major hemorrhage, the urgency of transfusion can exceed the need for compatibility testing against other blood group systems (and potentially Rh as well).[16] Also, blood compatibility testing beyond ABO and Rh is generally limited to antibody detection (not necessarily including forward typing). Still, in Europe, females who require blood transfusions are often typed for the K and extended Rh antigens to prevent sensitization to these antigens, which could put them at risk for developing hemolytic disease of the newborn during pregnancy.[17]
When needing to give red blood cell transfusion to a patient, the presence of clinically significant antibodies produced by the patient can be detected by mixing patient serum with 2 to 4 "screening" or "control" red blood cells that together display essentially all relevant antigens. If any of these mixes display a reaction (evidence of patient antibodies binding to the screening red blood cells), a more extensive antibody panel is warranted (as imaged at right).[18]
[Quoting Abstract: The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis, but it is also suspected to contribute to anticancer drug resistance, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(-) blood type identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Of note, Lan(-) (ABCB6(-/-)) individuals do not suffer any clinical consequences, although their deficiency in ABCB6 may place them at risk when determining drug dosage.]
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General concepts | |
Methods | |
Tests | |
Transfusion reactions and adverse effects | |
Blood group systems |