Ii antigen system

Adult red blood cells express I antigen abundantly.{{cite journal | vauthors = Yu LC, Lin M | title = Molecular genetics of the blood group I system and the regulation of I antigen expression during erythropoiesis and granulopoiesis | journal = Current Opinion in Hematology | volume = 18 | issue = 6 | pages = 421–6 | date = November 2011 | pmid = 21912254 | doi = 10.1097/MOH.0b013e32834baae9 | s2cid = 205827249 | url = http://ntur.lib.ntu.edu.tw/bitstream/246246/243345/-1/44.pdf }} 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.{{cite book | vauthors = Daniels G | chapter = I and i Antigens, and Cold Agglutination|date=2013-01-28 | title = Human Blood Groups |pages=469–484 |place=Oxford, UK |publisher=Wiley-Blackwell |doi=10.1002/9781118493595.ch25 |isbn=978-1-118-49359-5 }}

The I and i antigens are carbohydrate structures composed of repeating units of N-acetyllactosamine (LacNAc), and are located on the interior of structures carrying ABH and Lewis antigens. LacNAc repeats are made by the enzymes B3GNT1 and B4GALT1.{{Cite web|date=|title=OMIM Entry - # 110800 - BLOOD GROUP, I SYSTEM; Ii|url=https://www.omim.org/entry/110800|archive-url=|archive-date=|access-date=2021-01-31|website=www.omim.org|language=en-us}} 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 alleles; rather, I-branching enzyme converts i antigen to I antigen by adding branches.{{cite journal | vauthors = Pourazar A | title = Red cell antigens: Structure and function | journal = Asian Journal of Transfusion Science | volume = 1 | issue = 1 | pages = 24–32 | date = January 2007 | pmid = 21938229 | pmc = 3168130 | doi = 10.4103/0973-6247.28069 | doi-access = free }}{{cite journal | vauthors = Reid ME | title = The gene encoding the I blood group antigen: review of an I for an eye | journal = Immunohematology | year = 2020 | volume = 20 | issue = 4 | pages = 249–52 | doi = 10.21307/immunohematology-2019-458 | pmid = 15679458 | s2cid = 44662081 | url = https://www.redcrossblood.org/content/dam/redcrossblood/rcoassets/20_4_04.pdf }} The gene encoding I-branching enzyme is located on chromosome 6.

The function of I and i antigens are unknown but may be related to hematopoiesis, 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 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 and sickle cell disease.{{cite book | vauthors = Reid ME, Lomas-Francis C, Olsson ML |title=The Blood Group Antigen Facts Book|chapter=Ii Blood Group Collection|date=2012 |work=The Blood Group Antigen FactsBook |pages=651–653 |publisher=Elsevier |doi=10.1016/b978-0-12-415849-8.00037-5 |isbn=978-0-12-415849-8 }}

Transient autoantibodies against I antigen are common, especially after infection by Mycoplasma pneumoniae, and are rarely significant except in cold agglutinin disease. Transient antibodies against i antigen are common after infectious mononucleosis and are also not clinically significant. Antibodies which recognize both I and i antigens are termed anti-j antibodies.

{{Main articles|Cold agglutinin disease}}

The autoantibodies involved in cold agglutinin disease are usually against I antigen.{{cite journal | vauthors = Michalak SS, Olewicz-Gawlik A, Rupa-Matysek J, Wolny-Rokicka E, Nowakowska E, Gil L | title = Autoimmune hemolytic anemia: current knowledge and perspectives | journal = Immunity & Ageing | volume = 17 | issue = 1 | pages = 38 | date = November 2020 | pmid = 33292368 | pmc = 7677104 | doi = 10.1186/s12979-020-00208-7 | doi-access = free }} The antibodies are usually IgM (kappa subtype), unlike transient autoantibodies which are generally IgG. Cold-reactive IgM antibodies (cold agglutinins) bind to I antigen on red blood cells, and unlike IgG, are able to cause agglutination of red blood cells and activate complement to cause hemolysis, leading to anemia.

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 the GCNT2 gene which encodes the I-branching enzyme. These individuals have alloantibodies against the I antigen, though these are typically cold agglutinins and are unlikely to cause transfusion reactions.{{cite journal | vauthors = Poole J, Daniels G | title = Blood group antibodies and their significance in transfusion medicine | journal = Transfusion Medicine Reviews | volume = 21 | issue = 1 | pages = 58–71 | date = January 2007 | pmid = 17174221 | doi = 10.1016/j.tmrv.2006.08.003 }}

The adult i phenotype is associated with congenital cataracts, 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 of the lens, due to a mutation in the form of the I-branching enzyme which is expressed in lens epithelium, IGNTB.{{Cite web|title=OMIM Entry - * 600429 - GLUCOSAMINYL (N-ACETYL) TRANSFERASE 2, I-BRANCHING ENZYME; GCNT2|url=https://www.omim.org/entry/600429|access-date=2021-01-31|website=www.omim.org}}

The adult i phenotype is inherited in a recessive manner.

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

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, including chimpanzees and monkeys. This is not seen in non-primates: cats, dogs, or guinea pigs.

{{Reflist|30EM}}

• [https://web.archive.org/web/20121107214418/http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=i Ii] at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH

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Category:Blood antigen systems

Category:Transfusion medicine

Category:Genes on human chromosome 6