Junior blood group system

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ABCG2 (Junior blood group antigen)
Identifiers
SymbolABCG2
NCBI gene 9429
HGNC 74
OMIM 614490
UniProt Q9UNQ0
Other data
Locus Chr. 4 q22.1
Search for
Structures Swiss-model
Domains InterPro

The Junior blood group system (or JR) is a human blood group defined by the presence or absence of the Jr(a) antigen, a high-frequency antigen that is found on the red blood cells of most individuals. [1] People with the rare Jr(a) negative blood type can develop anti-Jr(a) antibodies, which may cause transfusion reactions and hemolytic disease of the newborn on subsequent exposures. Jr(a) negative blood is most common in people of Japanese heritage. [2]

Contents

Genetics

Autosomal recessive inheritance Autosomal recessive - en.svg
Autosomal recessive inheritance

The gene ABCG2 , located on chromosome 4q22.1, encodes an ATP-binding cassette transporter protein that carries the Jr(a) antigen. The Jr(a) negative blood type is inherited in an autosomal recessive manner: individuals who are homozygous for a null mutation of ABCG2 express this phenotype. [1] Homozygosity for certain missense mutations, or heterozygosity for a missense mutation and a null mutation, can result in a weak phenotype with decreased expression of Jr(a) antigen. [2] [3] As of 2018, over 25 null and weak alleles of ABCG2 have been described. [4]

Epidemiology

The highest rates of the Jr(a) negative blood type have been reported in Japan, [5] where its prevalence ranges from 1 in 60 in the Niigata region to 1 in 3800 in the Tokyo region. [1] Additionally, a number of cases have been documented in European Romani populations. [6] The Jr(a) negative blood type is very rare in America: a study of 9,545 Americans failed to identify any Jr(a) negative individuals. [5]

Clinical significance

Anti-Jr(a) antibodies are generally composed of Immunoglobulin G and develop when individuals are exposed to Jr(a) positive blood through pregnancy or blood transfusion. Some cases of anti-Jr(a) have been reported in patients who have not been previously transfused or pregnant. [2] [5]

Jr(a) is more strongly expressed on cord blood cells than on adult red blood cells, [4] and anti-Jr(a) has been reported to cause hemolytic disease of the newborn (HDN), [2] including fatal cases of HDN. [5] [7] The antibody has also been implicated in delayed hemolytic transfusion reactions. [2] However, the clinical significance of the antibody is variable: in some cases, individuals with anti-Jr(a) have been transfused with Jr(a) positive blood or given birth to Jr(a) positive babies without incident. It is recommended to transfuse individuals with anti-Jr(a) with Jr(a) negative blood if the antibody titer is high. In other cases, "least incompatible" blood (the blood unit that gives the weakest reactions during crossmatching) may be suitable. [5] [4] It is difficult to secure Jr(a) negative donor blood due to the rarity of this blood type. [6]

ABCG2 is a uric acid transporter, and the Jr(a) negative phenotype is associated with gout in Japanese populations. [8]

Laboratory testing

An individual's Junior blood type can be determined by serologic testing, which uses a monoclonal antibody reagent directed against the Jr(a) antigen. [6] DNA testing may be impractical due to the high number of mutations affecting Jr(a) expression. [9]

Anti-Jr(a) antibodies are most easily detected by the indirect antiglobulin test, and their reactivity is enhanced by enzyme treatment with ficin or papain. [2]

History

The Junior blood group system was discovered in 1970 by researchers Stroup and MacIllroy, who reported on five patients whose blood was incompatible with all samples tested except each other's. They named the causative antigen "JR" after Rose Jacobs, one of the five patients — the common name "Junior" is in fact a misnomer. [2]

In 2012, two research groups [6] [10] independently identified ABCG2 as the basis of the Junior blood group system. The Junior system was officially designated a blood group by the International Society of Blood Transfusion that year. [11]

Related Research Articles

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A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

<span class="mw-page-title-main">Duffy antigen system</span> Human blood group classification

Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD234, is a protein that in humans is encoded by the ACKR1 gene.

<span class="mw-page-title-main">Hemolytic disease of the newborn</span> Fetal and neonatal alloimmune blood condition

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis foetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells. The fetus can develop reticulocytosis and anemia. The intensity of this fetal disease ranges from mild to very severe, and fetal death from heart failure can occur. When the disease is moderate or severe, many erythroblasts are present in the fetal blood, earning these forms of the disease the name erythroblastosis fetalis.

<span class="mw-page-title-main">ABO blood group system</span> Classification of blood types

The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 44 different blood type classification systems currently recognized by the International Society of Blood Transfusions (ISBT) as of December 2022. A mismatch in this, or any other serotype, can cause a potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. The associated anti-A and anti-B antibodies are usually IgM antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses.

In ABO hemolytic disease of the newborn maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

Hemolytic disease of the newborn (anti-Kell1) is the second most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective.

Hemolytic disease of the newborn (anti-Rhc) can range from a mild to a severe disease. It is the third most common cause of severe HDN. Rh disease is the most common and hemolytic disease of the newborn (anti-Kell) is the second most common cause of severe HDN. It occurs more commonly in women who are Rh D negative.

The Kell antigen system is a human blood group system, that is, a group of antigens on the human red blood cell surface which are important determinants of blood type and are targets for autoimmune or alloimmune diseases which destroy red blood cells. The Kell antigens are K, k, Kpa, Kpb, Jsa and Jsb. The Kell antigens are peptides found within the Kell protein, a 93-kilodalton transmembrane zinc-dependent endopeptidase which is responsible for cleaving endothelin-3.

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<span class="mw-page-title-main">Rh blood group system</span> Human blood group system involving 49 blood antigens

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<span class="mw-page-title-main">P1PK blood group system</span> Human blood group system

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<span class="mw-page-title-main">Ii antigen system</span> Human blood group system

The Ii antigen system is a human blood group system based upon a gene on chromosome 6 and consisting of the I antigen and the i antigen. The I antigen is normally present on the cell membrane of red blood cells in all adults, while the i antigen is present in fetuses and newborns.

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<span class="mw-page-title-main">RHD (gene)</span> Protein-coding gene in the species Homo sapiens

Rh blood group, D antigen also known as Rh polypeptide 1 (RhPI) or cluster of differentiation 240D (CD240D) is a protein that in humans is encoded by the RHD gene.

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The Augustine blood group system is a human blood group system. It includes four red blood cell surface glycoprotein antigens which are encoded by alleles of the gene SLC29A1.

References

  1. 1 2 3 Kniffin CL (2013). "OMIM entry # 614490 – Blood Group, Junior System, Jr". Online Mendelian Inheritance in Man . Retrieved 1 September 2019.
  2. 1 2 3 4 5 6 7 Castilho L, Reid ME (2019). "A review of the JR blood group system". Immunohematology. 29 (2): 63–8. doi: 10.21307/immunohematology-2019-126 . PMID   24094238. S2CID   24659443.
  3. ↑ Hue-Roye K, Zelinski T, Cobaugh A, Lomas-Francis C, Miyazaki T, Tani Y, et al. (November 2013). "The JR blood group system: identification of alleles that alter expression". Transfusion. 53 (11): 2710–4. doi:10.1111/trf.12118. PMID   23438071. S2CID   2562261.
  4. 1 2 3 Moghaddam M, Naghi AA (2019). "Clinical significance of antibodies to antigens in the Raph, John Milton Hagen, I, Globoside, Gill, Rh-associated glycoprotein, FORS, JR, LAN, Vel, CD59, and Augustine blood group systems" (PDF). Immunohematology. 34 (3): 85–90. doi:10.21307/immunohematology-2018-013. PMID   30295501. S2CID   52933848.
  5. 1 2 3 4 5 Daniels G (2013). "Chapter 27: The Junior and Langereis blood group systems". Human Blood Groups (3rd ed.). West Sussex, UK: John Wiley & Sons. pp. 487–9. ISBN   978-1-118-49354-0.
  6. 1 2 3 4 Saison C, Helias V, Ballif BA, Peyrard T, Puy H, Miyazaki T, et al. (January 2012). "Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior". Nature Genetics. 44 (2): 174–7. doi:10.1038/ng.1070. PMC   3653631 . PMID   22246505.
  7. ↑ Kim MS, Kim JS, Park H, Chung Y, Kim H, Ko DH, et al. (July 2019). "Fatal hemolytic disease of the fetus and newborn caused by anti-Jra antibody: A case report and literature review". Transfusion and Apheresis Science. 59 (1): 102605. doi: 10.1016/j.transci.2019.06.029 . PMID   31324575.
  8. ↑ Silberstein LE, Anastasi J (14 June 2017). "Part XI: Transfusion medicine". Hematology: Basic Principles and Practice E-Book (7th ed.). Elsevier Health Sciences. p. 1700. ISBN   978-0-323-50971-8.
  9. ↑ Haer-Wigman L, Ait Soussan A, Ligthart P, de Haas M, van der Schoot CE (July 2014). "Molecular analysis of immunized Jr(a-) or Lan- patients and validation of a high-throughput genotyping assay to screen blood donors for Jr(a-) and Lan- phenotypes". Transfusion. 54 (7): 1836–46. doi:10.1111/trf.12544. PMID   24456066. S2CID   3229027.
  10. ↑ Zelinski T, Coghlan G, Liu XQ, Reid ME (January 2012). "ABCG2 null alleles define the Jr(a-) blood group phenotype". Nature Genetics. 44 (2): 131–2. doi:10.1038/ng.1075. PMID   22246507. S2CID   20854378.
  11. ↑ Storry JR (2014). "Five new blood group systems - what next?". ISBT Science Series. 9 (1): 136–140. doi:10.1111/voxs.12078. ISSN   1751-2816. S2CID   84328440.
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