The Junior blood group system (or JR) is a human

blood group A blood type (also known as a blood group) 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 ...

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. People with the rare Jr(a) negative blood type can develop anti-Jr(a) antibodies, which may cause

transfusion reaction Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used w ...

s and

hemolytic disease of the newborn 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 (one of the five ...

on subsequent exposures. Jr(a) negative blood is most common in people of Japanese heritage.

Genetics

The gene ''

ABCG2 ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ''ABCG2'' gene. ABCG2 has also been designated as CDw338 (cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs a ...

'', located on chromosome 4q22.1, encodes an

ATP-binding cassette transporter The ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC transp ...

protein that carries the Jr(a) antigen. The Jr(a) negative blood type is inherited in an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

manner: individuals who are

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

for a

null mutation A null allele is a nonfunctional allele (a variant of a gene) caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the alle ...

of ''ABCG2'' express this phenotype. Homozygosity for certain

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

s, or heterozygosity for a missense mutation and a null mutation, can result in a weak phenotype with decreased expression of Jr(a) antigen. As of 2018, over 25 null and weak alleles of ''ABCG2'' have been described.

Epidemiology

The highest rates of the Jr(a) negative blood type have been reported in Japan, where its prevalence ranges from 1 in 60 in the Niigata region to 1 in 3800 in the

Tokyo Tokyo (; ja, 東京, , ), officially the Tokyo Metropolis ( ja, 東京都, label=none, ), is the capital and largest city of Japan. Formerly known as Edo, its metropolitan area () is the most populous in the world, with an estimated 37.468 ...

region. Additionally, a number of cases have been documented in European

Romani Romani may refer to: Ethnicities * Romani people, an ethnic group of Northern Indian origin, living dispersed in Europe, the Americas and Asia ** Romani genocide, under Nazi rule * Romani language, any of several Indo-Aryan languages of the Roma ...

populations. 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.

Clinical significance

Anti-Jr(a) antibodies are generally composed of

Immunoglobulin G Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...

and develop when individuals are exposed to Jr(a) positive blood through pregnancy or

blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

. Some cases of anti-Jr(a) have been reported in patients who have not been previously transfused or pregnant. Jr(a) is more strongly expressed on

cord blood Cord blood (umbilical cord blood) is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders su ...

cells than on adult red blood cells, and anti-Jr(a) has been reported to cause

(HDN), including fatal cases of HDN. The antibody has also been implicated in delayed hemolytic transfusion reactions. 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 Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...

is high. In other cases, "least incompatible" blood (the blood unit that gives the weakest reactions during

crossmatching Cross-matching or crossmatching is a test performed before a blood transfusion as part of blood compatibility testing. Normally, this involves adding the recipient's blood plasma to a sample of the donor's red blood cells. If the blood is incom ...

) may be suitable. It is difficult to secure Jr(a) negative donor blood due to the rarity of this blood type. ABCG2 is a

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...

transporter, and the Jr(a) negative phenotype is associated with

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensit ...

in Japanese populations.

Laboratory testing

An individual's Junior blood type can be determined by serologic testing, which uses a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

reagent directed against the Jr(a) antigen.

DNA test Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

ing may be impractical due to the high number of mutations affecting Jr(a) expression. Anti-Jr(a) antibodies are most easily detected by the

indirect antiglobulin test A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood ...

, and their reactivity is enhanced by enzyme treatment with

ficin Ficain also known as ficin, debricin, or higueroxyl delabarre () is a proteolytic enzyme extracted from the latex sap from the stems, leaves, and unripe fruit of the American wild fig tree ''Ficus insipida''. Ficain was originally called ficin, a ...

papain Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family. It has wide ...

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. In 2012, two research groups 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 The International Society of Blood Transfusion (ISBT) is a scientific society founded in 1935, which promotes the study of blood transfusion and spreads reliable information about the ways in which blood transfusion medicine and science can bes ...

that year.

References

{{Transfusion medicine Genes on human chromosome 4 Blood antigen systems Transfusion medicine