Transfusion medicine
Red blood cell antigens
Ii system
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PubMed Search: Ii antigens / I blood group system
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Transmission | Laboratory | Case reports | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Adkins BD, Booth GS. Ii system. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedicineii.html. Accessed April 1st, 2025.
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
Terminology
- I: antigen in I blood group system
- i: antigen in Ii collection
Pathophysiology
- Antigens are formed by repeating lactosamines associated with ABH antigens on red cell surfaces (Fung: Technical Manual, 19th Edition, 2017)
- i antigen is linear and less complex
- I is larger and more complex with branching
- I gene is GCNT2 and has multiple tissue specific isoforms (Immunohematology 2019;35:85)
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
Transmission
- Antibodies are naturally occurring
Laboratory
- 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
- 8 year old girl with EBV presenting with hemolytic anemia and anti-i antibodies (J Pediatr Hematol Oncol 2019;41:324)
- 56 year old woman and 73 year old man presenting with ABO backtyping issues associated with cold antibodies (J Clin Lab Anal 2021;35:e23894)
- 70 year old man with cold agglutinin disease and COVID-19 treated with therapeutic plasma exchange (BMJ Case Rep 2021;14:e244227)
- 78 year old man with cold agglutinin disease presenting with dry gangrene (Rheumatology (Oxford) 2021 Aug 13 [Epub ahead of print])
Additional references
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?
- Babesiosis
- EBV
- Mycoplasma
- Parvovirus
Board review style answer #1
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?
- Donath Landsteiner
- Ham test
- Thermal amplitude
- Type and screen
Board review style answer #2
