The Ii antigen system is a

human blood group system 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 (gene ...

based upon a gene on

chromosome 6 Chromosome 6 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 6 spans nearly 171 million base pairs (the building material of DNA) and represents between 5.5 and 6% of the total DNA i ...

and consisting of the I antigen and the i antigen. The I antigen is normally present on the cell membrane of

red blood cells Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

in all adults, while the i antigen is present in

fetuses A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...

and newborns.

I and i antigens

Adult red blood cells express I antigen abundantly. Developing fetuses and newborns express i antigen until around 13-20 months after birth, when I antigen starts to be expressed instead. Like ABH antigens, which make up the ABO blood group, I and i antigens are not restricted to the red blood cell membrane, but are found on most human cells and in body fluids such as

saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...

. The I and i antigens are

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

structures composed of repeating units of ''N''-acetyllactosamine (LacNAc), and are located on the interior of structures carrying ABH and

Lewis Lewis may refer to: Names * Lewis (given name), including a list of people with the given name * Lewis (surname), including a list of people with the surname Music * Lewis (musician), Canadian singer * " Lewis (Mistreated)", a song by Radiohe ...

antigens. LacNAc repeats are made by the enzymes B3GNT1 and

B4GALT1 Beta-1,4-galactosyltransferase 1 is an enzyme that in humans is encoded by the ''B4GALT1'' gene. This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have excl ...

. The i antigen is made of linear repeats, while the structure of the I antigen is branched. Unlike most other blood groups, the two antigens are not encoded by different

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

s; rather, I-branching enzyme converts i antigen to I antigen by adding branches. The gene encoding I-branching enzyme is located on chromosome 6.

Clinical significance

The function of I and i antigens are unknown but may be related to

hematopoiesis Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...

, the production of blood. The rapid conversion from i to I antigens after birth suggests that I antigen plays an important role in adult red blood cells. The presence of the linear i antigen in fetuses, rather than the branched I antigen, may have developed as an

evolutionary Evolution is the change in the heritable characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, resulting in certa ...

mechanism to prevent ABO hemolytic disease of the fetus and newborn. Enhanced expression of i antigen is associated with conditions involving stress hematopoiesis such as

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

and

sickle cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...

. Transient

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

against I antigen are common, especially after infection by ''

Mycoplasma pneumoniae ''Mycoplasma pneumoniae'' is a species of very small-cell bacteria that lack a cell wall, in the class Mollicutes. ''M. pneumoniae'' is a human pathogen that causes the disease Mycoplasma pneumonia, a form of atypical bacterial pneumonia related ...

'', and are rarely significant except in

cold agglutinin disease Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below , directed again ...

. Transient antibodies against i antigen are common after

infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adu ...

and are also not clinically significant. Antibodies which recognize both I and i antigens are termed anti-j antibodies.

Cold agglutinin disease

The autoantibodies involved in cold agglutinin disease are usually against I antigen. The antibodies are usually

IgM Immunoglobulin M (IgM) is the largest of several isotypes of antibodies (also known as immunoglobulin) that are produced by vertebrates. IgM is the first antibody to appear in the response to initial exposure to an antigen; causing it to also ...

(

kappa Kappa (; uppercase Κ, lowercase κ or cursive ; , ''káppa'') is the tenth letter of the Greek alphabet, representing the voiceless velar plosive sound in Ancient and Modern Greek. In the system of Greek numerals, has a value of 20. It was d ...

subtype), unlike transient autoantibodies which are generally

IgG 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 ant ...

. Cold-reactive IgM antibodies ( cold agglutinins) bind to I antigen on red blood cells, and unlike IgG, are able to cause

agglutination In linguistics, agglutination is a morphology (linguistics), morphological process in which words are formed by stringing together morphemes (word parts), each of which corresponds to a single Syntax, syntactic feature. Languages that use agglu ...

of red blood cells and activate

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 ...

to cause

hemolysis Hemolysis or haemolysis (), also known by #Nomenclature, several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may ...

, leading to

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

Adult i phenotype

Rarely, individuals have the i antigen on their red blood cells into adulthood, known as the adult i phenotype. This is due to the presence of a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

in the GCNT2 gene which encodes the I-branching enzyme. These individuals have

alloantibodies Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility an ...

against the I antigen, though these are typically cold agglutinins and are unlikely to 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 ...

. The adult i phenotype is associated with

congenital cataract Congenital cataracts are a lens opacity that is present at birth. Congenital cataracts occur in a broad range of severity. Some lens opacities do not progress and are visually insignificant, others can produce profound visual impairment. Cong ...

s, most markedly in Japanese and Taiwanese people and least markedly in Caucasian people. Cataracts occur when i antigen rather than I antigen is present on the

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

of the

lens A lens is a transmissive optical device that focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements'') ...

, due to a mutation in the form of the I-branching enzyme which is expressed in lens epithelium, IGNTB. The adult i phenotype is inherited in a

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 ...

manner.

History

The I antigen was first described in 1956 and the i antigen was discovered in 1960. I and i were the first discovered antigens which change significantly during

human development Human development may refer to: * Development of the human body ** This includes physical developments such as growth, and also development of the brain * Developmental psychology * Development theory * Human development (economics) * Human Develo ...

. The letter I was chosen to reflect the "individuality" of a person studied who lacked the I antigen.

Other species

A similar blood group system with a developmental change resembling the Ii system (with human neonatal cells expressing i antigen and adult cells expressing I antigen) has been observed in most

primates Primates is an order of mammals, which is further divided into the strepsirrhines, which include lemurs, galagos, and lorisids; and the haplorhines, which include tarsiers and simians ( monkeys and apes). Primates arose 74–63 ...

, including

chimpanzees The chimpanzee (; ''Pan troglodytes''), also simply known as the chimp, is a species of great ape native to the forests and savannahs of tropical Africa. It has four confirmed subspecies and a fifth proposed one. When its close relative the ...

and

monkeys Monkey is a common name that may refer to most mammals of the infraorder Simiiformes, also known as simians. Traditionally, all animals in the group now known as simians are counted as monkeys except the apes. Thus monkeys, in that sense, co ...

. This is not seen in non-primates:

cats The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...

dogs The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the gray wolf. Also called the domestic dog, it was selectively bred from a population of wolves during the Late Pleistocene by hunter-gatherers ...

, or

guinea pigs The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy ( ), is a species of rodent belonging to the genus ''Cavia'', family Caviidae. Breeders tend to use the name "cavy" for the animal, but "gui ...

References

External links

Ii
at

BGMUT The BGMUT (Blood Group antigen gene MUTation) Database documents allele, allelic variations in the genes encoding for human blood group systems. It was set up in 1999 through an initiative of the Human Genome Variation Society (HGVS). Since 2006, i ...

Blood Group Antigen Gene Mutation Database at

NCBI The National Center for Biotechnology Information (NCBI) is part of the National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is loca ...

NIH The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

{{transfusion medicine Blood antigen systems Transfusion medicine Genes on human chromosome 6