Human blood group systems explained

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 .^[2]

Table of systems and classifications

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 P^k
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, Kp^a, Kp^b, Js^a and Js^b ^[4]
007	Lewis	LE	Carbohydrate (fucose residue).	19p13.3	Mainly Le^a and Le^b	Associated with tissue ABH antigen secretion.
008	Duffy	FY	Protein (chemokine receptor).	1q23.2	Mainly Fy^a and Fy^b	Individuals lacking Duffy antigens altogether are immune to malaria caused by Plasmodium vivax and Plasmodium knowlesi.
009	Kidd	JK	Protein (urea transporter).	18q12.3	Jk^a and Jk^b
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.	9p13.3
030	Rh-associated glycoprotein	RHAg	Rh-associated glycoprotein.	6p21-qter
031	Forssman	FORS	Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	9q34.13
032	Langereis^[5]	LAN	ABCB6, human ATP-binding cassette (ABC) transporter, mitochondrial porphyrin transporter.	2q36
033	Junior	JR	ABCG2. Multi-drug transporter protein.	4q22
034	Vel	Vel	Human red cell antigens.	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		Er^a, Er^b, 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

Antibodies

Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems:^[10]

										Ii
Most common in immediate hemolytic transfusion reactions	A		Yes	Fy^a	Jk^a
Most common in delayed hemolytic transfusion reactions		E,D,C			Jk^a
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	Le^a, Le^b	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 and papain				Fy^a, Fy^b		Yes	Yes
Displaying dosage		Cc, Ee		Yes	Yes		Yes

Compatibility testing

See main article: Blood compatibility testing.

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]

Further reading

• Book: Dean, Laura . 2005 . Blood Groups and Red Cell Antigens . Bethesda, MD, USA . National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health . 19 February 2016 .
• Book: SIB-EBI-PIR . 2016 . Swiss-Prot Protein Knowledgebase . Blood group Antigen Proteins: List of Entries, 17 February version . Geneva, CHE . Swiss Institute of Bioinformatic (SIB), in cooperation with the European Bioinformatics Institute (EBI, Hinxton, ENG), and the Protein Information Resource (PIR, Washington DC, USA) . https://www.uniprot.org/docs/bloodgrp.txt . 19 February 2016 .
• ISBT Table of blood group antigens within systems, updated August 2008.
• BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH.

External links

• BGvar, a comprehensive online resource for blood group associated genetic variants.
  - Rophina. Mercy. Pandhare. Kavita. Jadhao. Sudhir. Nagaraj. Shivashankar H.. Scaria. Vinod. 2021-02-05. BGvar - a comprehensive resource for blood group immunogenetics. bioRxiv. 32 . 3 . en. 229–236. 10.1101/2021.02.04.429861. 34897852. 231885707.

Notes and References

1. Web site: ISBT . 2016 . International Society for Blood Transfusion (ISBT) Committee on Terminology for Red Cell Surface Antigens, Terminology Home Page . 20 February 2016 . https://web.archive.org/web/20160303182049/https://ibgrl.blood.co.uk/ISBT%20Pages/ISBT%20Terminology%20Pages/Terminology%20Home%20Page.htm . 3 March 2016 . dead .
2. Web site: Red Cell Immunogenetics and Blood Group Terminology. International Society of Blood Transfusion. 2023. https://web.archive.org/web/20220202131327/https://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/. 2 February 2022. 25 April 2023. live.
3. Web site: Table of Blood Group Systems v 10.0 (June 2021). ISBT. 2021. International Society of Blood Transfusion. live. https://web.archive.org/web/20220115164429/https://www.isbtweb.org/fileadmin/user_upload/Table_of_blood_group_systems_v10.0_30-JUN-2021_with_LRG_and_revised_antigens.pdf. 15 January 2022. 11 February 2022.
4. Smart. E.. Armstrong. B.. Blood group systems. ISBT Science Series. 3. 2. 2008. 68–92. 1751-2816. 10.1111/j.1751-2824.2008.00188.x. free.
5. Helias, V. . Saison, C. . Ballif, B.A. . Peyrard, T. . Takahashi, J. . Takahashi, H. . Tanaka, M. . Deybach, J.C. . Puy, H. . Le Gall, M. . Sureau, C. . Pham, B.N. . Le Pennec, P.Y. . Tani, Y. . Cartron, J.P. . Arnaud, L. . 2012 . ABCB6 is Dispensable for Erythropoiesis and Specifies the New Blood Group System Langereis . Nature Genetics . 44 . 2, January 15 . 170–173 . 10.1038/ng.1069 . 3664204 . 22246506 . [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.] .
6. Daniels . G. . Ballif . B. A. . Helias . V. . Saison . C. . Grimsley . S. . Mannessier . L. . Hustinx . H. . Lee . E. . Cartron . J.-P. . Peyrard . T. . Arnaud . L. . Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization . Blood . 20 April 2015 . 125 . 23 . 3651–3654 . 10.1182/blood-2015-03-631598 . 25896650 . 8 . 4458803.
7. National Center for Global Health and Medicine, Japanese Red Cross Society, Fukushima Medical University and Japan Agency for Medical Research and Development (2019-08-05) 新たなヒト血液型「KANNO」の国際認定―国立国際医療研究センターなど、日本の研究グループとして初めての登録― (in Japanese)
8. "Omae, Y.; Ito, S.; Takeuchi, M.; Isa, K.; Ogasawara, K.; Kawabata, K.; Oda, A.; Kaito, S.; Tsuneyama, H.; Uchikawa, M.; Wada, I.; Ohto, H.; Tokunaga, K. (2019). "Integrative genome analysis identified the KANNO blood group antigen as prion protein" Transfusion. 2019 Jul;59(7):2429-2435. DOI:10.1111/trf.15319. Epub 2019 Apr 24.
9. Karamatic Crew . Vanja . Tilley . Louise A . Satchwell . Timothy J . AlSubhi . Samah A . Jones . Benjamin . Spring . Frances A . Walser . Piers J . Martins Freire . Catarina . Murciano . Nicoletta . Rotordam . Maria Giustina . Woestmann . Svenja J . Hamed . Marwa . Alradwan . Reem . AlKhrousey . Mouza . Skidmore . Ian . Lewis . Sarah . Hussain . Shimon . Jackson . Jane . Latham . Tom . Kilby . Mark D . Lester . William Arthur . Becker . Nadine . Rapedius . Markus . Toye . Ashley Mark . Thornton . Nicole M . Missense mutations in PIEZO1, encoding the Piezo1 mechanosensor protein, define the Er red blood cell antigens . . 19 September 2022 . 141 . 2 . 135–146 . 10.1182/blood.2022016504 . 36122374 . 252382544 . free . 10644042 .
10. Book: Mais, Daniel . Quick compendium of clinical pathology . American Society for Clinical Pathology Press . United States . 2014 . 978-0-89189-615-9 . 895712380 .
11. Hill. Ben C.. Hanna. Courtney A.. Adamski. Jill. Pham. Huy P.. Marques. Marisa B.. Williams. Lance A.. Ficin-Treated Red Cells Help Identify Clinically Significant Alloantibodies Masked as Reactions of Undetermined Specificity in Gel Microtubes. Laboratory Medicine. 48. 1. 2017. 24–28. 0007-5027. 10.1093/labmed/lmw062. 28007780. free.
12. Web site: Questions and Answers on Proteolytic Enzymes Used in Blood Group Serology. Canadian Society for Transfusion Medicine. Eric Ching. 2021-01-28.
13. Web site: American Association for Clinical Chemistry. Blood Typing. 15 November 2019. 27 January 2020. Lab Tests Online. American Association for Clinical Chemistry.
14. ABO Grouping: Overview, Clinical Indications/Applications, Test Performance . Gonsorcik, V.K. . . 7 August 2018 . 2 March 2020 .
15. Bacigalupo. A.. Van Lint. M. T.. M. Margiocco. D. Occhini. Ferrari. G.. Pittaluga. P. A.. Frassoni. F.. Peralvo. J.. Lercari. G.. Carubia. F.. Marmont. A. M.. Abo Compatibility and Acute Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation. Transplantation. 45. 6. 1988. 1091–1093. 0041-1337. 10.1097/00007890-198806000-00018. 3289150. 39707395. free.
16. Goodell. Pamela P.. Uhl. Lynne. Mohammed. Monique. Powers. Amy A.. Risk of Hemolytic Transfusion Reactions Following Emergency-Release RBC Transfusion. American Journal of Clinical Pathology. 134. 2. 2010. 202–206. 0002-9173. 10.1309/AJCP9OFJN7FLTXDB. 20660321. free.
17. Westhoff. Connie M.. Blood group genotyping. Blood. 133. 17. 2019. 1814–1820. 0006-4971. 10.1182/blood-2018-11-833954. 30808639. free.
18. Web site: Glossary: Antibody Screen - Blood Bank Guy Glossary .