Transfusion medicine

Red blood cell antigens

Ii system

Editorial Board Member: Kyle Annen, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.

Last author update: 25 April 2022
Last staff update: 15 January 2024

Copyright: 2022,, Inc.

PubMed Search: Ii antigens / I blood group system

Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.
Page views in 2023: 378
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Cite this page: Adkins BD, Booth GS. Ii system. website. Accessed February 22nd, 2024.
Definition / general
  • Ii antigens are carbohydrate antigens formed from multiple ABO moieties
  • Cold reacting antibodies
Essential features
  • Cold autoantibodies associated with infection
  • Generally, not clinically significant
  • Can cause cold agglutinin disease
  • I: antigen in I blood group system
  • i: antigen in Ii collection
Clinical features
  • i is present in younger patients, with branching and complexity being added with age, and is converted to I antigens by 13 - 20 months of age
  • Antibodies common with infection:
    • Transient anti-i seen in infectious mononucleosis (EBV)
    • Transient anti-I seen in Mycoplasma infection
  • Antigens (type: carbohydrate) (Fung: Technical Manual, 19th Edition, 2017)
  • I: larger and more complex, found in the RBC cell membrane of all adults
  • i: small and linear without branching, found in fetus and infants
    • Cord cells characteristically lack I
  • Autoantibodies:
    • Generally naturally occurring and not clinically significant
    • Cold agglutinin disease associated with antibodies (usually IgM against I antigen) that have high thermal amplitude and can react near body temperature, a common cause of acquired hemolytic anemia
    • Disease associations (Immunohematology 2019;35:85):
      • GCNT2 mutations can cause adult i phenotype and are associated with congenital cataracts
      • Decreased GCNT2 expression associated with melanoma progression
      • Increased GCNT2 expression in leukemia / lymphoma cells associated with increased clearance by NK cells
  • Antibodies are naturally occurring
  • May be present at immediate spin, leading to ABO mismatch and challenges in pretransfusion testing
  • Antibodies common when testing at 4 °C
  • Thermal amplitude study assesses the reactivity of serum or plasma with RBCs at different temperatures, typically 40 °C, 220 °C, 300 °C and 370 °C
    • Reactivity at > 30 °C is clinically significant; the closer to body temperature clumping occurs, the more harmful the patient’s cold agglutinins are
    • In patients undergoing cardioplegia where the body temperature is lowered, it is important to know the exact temperature of reactivity
    • Direct antiglobulin test (DAT) may be utilized to screen for cold agglutinin disease
  • Reference: Fung: Technical Manual, 19th Edition, 2017
Case reports
Board review style question #1
A patient is found to have an i antibody. The patient is a 14 year old boy presenting to his primary care physician for fatigue and was found to be anemic. What infectious process may be causing this finding?

  1. Babesiosis
  2. EBV
  3. Mycoplasma
  4. Parvovirus
Board review style answer #1

Comment Here

Reference: Ii
Board review style question #2
A patient is preparing for cardiothoracic surgery and will be receiving cardioplegia. What lab test may help prevent hemolysis in this patient?

  1. Donath Landsteiner
  2. Ham test
  3. Thermal amplitude
  4. Type and screen
Board review style answer #2
C. Thermal amplitude

Comment Here

Reference: Ii
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