The Lan blood group system (short for Langereis) is a human blood group 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, can produce an anti-Lan

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

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 ...

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 fetalis, 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, an

ATP-binding cassette transporter The ABC transporters, ATP synthase (ATP)-binding cassette 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 Phyl ...

encoded by the ''ABCB6'' gene on chromosome 2q36. The Lan-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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

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. Mos ...

for nonfunctional

alleles An allele is a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule. Alleles can differ at a single position through single nucleotide polymorphisms (SNP), but they can also have insertions and deletions ...

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 (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...

synthesis and

porphyrin Porphyrins ( ) are heterocyclic, macrocyclic, organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (). In vertebrates, an essential member of the porphyrin group is heme, w ...

transport and is widely expressed throughout the body, particularly in the heart,

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

, eye, fetal liver,

mitochondrial membrane A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

, 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 Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

. 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 ...

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 ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans and is the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mos ...

'' ''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 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 positi ...

is high. One case of

autoimmune hemolytic anemia Autoimmune hemolytic anemia (AIHA) occurs when a person's immune system produces antibodies directed against their own red blood cells (RBCs). These antibodies attach to red cells, causing them to break down ( lyse), and reducing the number of ox ...

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 Immunoglobulin G (IgG) 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 ...

and may bind

complement Complement may refer to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class collections into complementary sets * Complementary color, in the visu ...

. 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 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 wi ...

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

, 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 provides information about the ways in which blood transfusion medicine and science can best serve p ...

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