The Lan blood group system (short for Langereis) 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 Lan antigen on a person's red blood cells. More than 99.9% of people are positive for the Lan antigen. Individuals with the rare Lan-negative blood type, which is a

recessive trait 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 ...

, can produce an anti-Lan

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

when exposed to Lan-positive blood. Anti-Lan antibodies may cause

transfusion reactions 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 mod ...

on subsequent exposures to Lan-positive blood, and have also been implicated in mild cases of

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 ...

. However, the clinical significance of the antibody is variable. The antigen was first described in 1961, and Lan was officially designated a blood group in 2012.

Molecular biology

The Lan antigen is carried on the protein

ABCB6 ATP-binding cassette super-family B member 6, mitochondrial is a protein that in humans is encoded by the ''ABCB6'' gene. The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporte ...

, an

ATP-binding cassette transporter The ATP synthase, ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene family, gene families. It is represented in all extant taxon, extant Phylum ...

encoded by the ''ABCB6'' gene on chromosome 2q36. The Lan-negative blood type is inherited in an autosomal recessive manner, being expressed by 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 nonfunctional

alleles An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...

of ''ABCB6''. Some variant alleles cause a weak positive phenotype, which may be mistaken for a Lan-negative phenotype in serologic testing. As of 2018, more than 40 null or weak alleles of ''ABCB6'' have been described. ABCB6 is involved in

heme Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver. In biochemical terms, heme is a coordination complex "consis ...

synthesis and

porphyrin Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical com ...

transport and is widely expressed throughout the body, particularly in the heart, skeletal muscle, eye, fetal liver, mitochondrial membrane, and

Golgi bodies The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles in ...

. The Lan antigen 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 s ...

cells than on adult red blood cells. Despite the protein's wide distribution, Lan-negative individuals do not appear to experience any adverse effects from the absence of ABCB6. It is thought that other porphyrin transporters, such as ABCG2 (which carries the Junior blood group antigen), may compensate. A 2018 study found that Lan-negative blood cells exhibited resistance to '' Plasmodium falciparum'' ''in vitro''.

Epidemiology

The prevalence of the Lan antigen exceeds 99.9% in most populations. The frequency of the Lan-negative blood type is estimated at 1 in 50,000 in Japanese populations, 1 in 20,000 in Caucasians, and 1 in 1,500 in black people from South Africa.

Clinical significance

When Lan-negative individuals are exposed to Lan-positive blood through transfusion or pregnancy, they may develop an anti-Lan antibody. Anti-Lan is considered a clinically significant antibody, but its effects are variable. It has been associated with severe

and mild cases of

, but in some cases individuals with the antibody have not experienced any adverse effects from exposure to Lan-positive blood. It is recommended that individuals with anti-Lan are transfused with Lan-negative blood, especially if the antibody titer is high. One case of

autoimmune hemolytic anemia Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...

involving auto-anti-Lan has been described.

Laboratory testing

Serologic reagents and molecular assays for Lan antigen typing were not commercially available as of 2013. Anti-Lan antibodies are typically composed of immunoglobulin G and may bind

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...

. As an IgG antibody, anti-Lan can be detected using the indirect antiglobulin test. The antibody is resistant to 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,

trypsin Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the d ...

, DTT, and EDTA/glycine-acid.

History

The Lan antigen was first described in 1961 by Van der Hart et al., when a Dutch patient suffered a severe hemolytic transfusion reaction. The patient was found to produce an antibody that reacted with all but 1 out of 4,000 blood donors tested. The causative antigen was identified and designated "Langereis" after the patient's last name. Lan 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 ...

in 2012, following the discovery of the molecular basis of the Lan-negative phenotype.

References

{{Transfusion medicine Blood antigen systems Transfusion medicine Genes on human chromosome 2