MIDTERM LECTURE 1: I BLOOD GROUP Flashcards
What is the main characteristic of cold agglutinins?
Cold agglutinins cause red blood cells to clump together (agglutinate) at cold temperatures.
What blood condition is associated with cold agglutinins?
Acquired hemolytic anemia.
When was the I antigen first named, and by whom?
In 1956 by Wiener and coworkers.
What does the “I” in the I antigen stand for?
Individuality
What was originally believed about individuals whose blood did not react with anti-I?
They were thought to be homozygous for a rare gene that produced the “i” antigen.
What was the term given to adults lacking the I antigen?
The “adult i” phenotype.
Who first reported the existence of anti-i?
Marsh and Jenkins.
In what year was anti-i discovered?
1960
What did the discovery of anti-i reveal about the relationship between I and i?
It helped establish that they were structurally related but not antithetical antigens.
According to ISBT, what are the correct names for these I blood group antigens?
“I adult” and “i adult.”
Are I and i antithetical antigens?
No, they are structurally different carbohydrate chains.
What type of carbohydrate structure does the I antigen have?
Branched carbohydrate chains.
What type of carbohydrate structure does the i antigen have?
Linear carbohydrate chains.
What enzyme is responsible for converting i-active straight chains into I-active branched chains?
glycosyl transferase
Has the gene encoding the glycosyl transferase responsible for I antigen conversion been cloned?
Yes
What causes the rare adult i phenotype?
Mutations in the gene responsible for converting i into I
Does the same gene control the production of the i antigen?
No, the synthesis of i antigen is not controlled by the gene that converts i to I.
What is the ISBT system number for the I blood group system?
027
What is the ISBT collection number for the Ii collection?
207
What is the ISBT antigen number for the I antigen?
027001.
What is the ISBT antigen number for the i antigen?
207002
Why is there potential confusion in ISBT terminology regarding I and i antigens?
Because both the I system and the Ii collection use the symbol “I,” with antigen numbers distinguishing them.
How are I and i antigens related in terms of prevalence?
Both are common, but their levels change as a person grows.
Which antigen is more abundant at birth?
i antigen
How does the expression of I and i change over time?
i decreases while I increases
when does I reach adult levels
18 months
Which antigen is predominant in adult RBCs?
I antigen, with only trace amounts of i antigen remaining.
Is there a true I-negative (I–) or i-negative (i–) phenotype?
No, the levels of I and i vary in each person.
What factor influences the detection of I and i on RBCs?
The specific anti-I or anti-i antibody used in testing.
How is i antigen reactivity related to marrow transit time and RBC age?
i reactivity on RBCs is inversely proportional to marrow transit time and RBC age
What happens in rare cases where individuals do not follow the typical Ii antigen transition?
They remain i-positive throughout life, developing the rare “i adult” phenotype.
How does i expression in i adult RBCs compare to cord RBCs?
i adult RBCs express more i antigen than cord RBCs.
What is used to enhance the reactivity of I and i antigens with their respective antibodies?
Treatment with ficin and papain.
Which chemical treatments do the I and i antigens resist?
DTT (dithiothreitol) and glycine-acid EDTA.
What type of antibody is Anti-I?
A common autoantibody found in almost all sera.
How can Anti-I be detected?
By testing at 4°C and/or using enzyme-treated RBCs.
How does classic Anti-I react with different RBC types?
Strongly agglutinates adult RBCs but reacts weakly or not at all with cord or adult i RBCs.
Is autoanti-I harmful?
No, it is benign and does not cause RBC destruction.
antibody class of benign autoanti-I
weak, naturally occuring IgM
titer of benign autoanti-I
less than 64 at 4°C
How can testing conditions enhance Anti-I detection?
Cold incubation
albumin
enzyme methods
and slightly acidified serum
How can benign autoanti-I cause issues in pretransfusion testing?
It can interfere with testing at room temperature and may bind complement.
How can cold-reactive antibodies be avoided in pretransfusion testing?
By avoiding room temperature testing, using anti-IgG instead of polyspecific AHG, or performing cold autoadsorption.
What condition is associated with pathogenic autoanti-I?
Cold agglutinin disease (CAD).
What makes pathogenic autoanti-I different from benign autoanti-I?
It is a strong IgM antibody with a high titer and broad thermal range (reacts up to 30°C).
What symptoms can pathogenic autoanti-I cause?
Autoagglutination, peripheral vascular occlusion (acrocyanosis), and hemolytic anemia.
How does pathogenic Anti-I react with RBCs?
It reacts equally well with adult and cord RBCs at room temperature and 4°C.
How can strong cold autoantibodies complicate pretransfusion testing?
They can mask underlying alloantibodies and interfere with blood typing.
What microorganism can stimulate autoanti-I production?
Mycoplasma pneumoniae, which can cause strong cold agglutinins and hemolysis.
In which individuals is alloanti-I found?
In people with the i adult phenotype.
Why does alloanti-I not react with autologous RBCs?
Because i adult RBCs are not completely devoid of the I antigen.
How are i adult individuals traditionally transfused?
With i adult units, though this may not always be necessary.
Why is Anti-I not associated with HDFN?
It is an IgM antibody, and I antigen is weakly expressed on infant RBCs.
Has alloanti-i ever been described?
No, alloanti-i has never been reported.
What type of antibody is autoanti-i?
A rare IgM antibody that reacts strongly with cord and i adult RBCs but weakly with I adult RBCs.
At what temperature does autoanti-i react best?
4°C with saline-suspended cells.
Why is autoanti-i rarely detected in routine testing?
Because standard test cells (except cord RBCs) have poor i antigen expression.
Is autoanti-i common in healthy individuals?
No, unlike anti-I, autoanti-i is not commonly found in healthy individuals.
Which conditions are associated with potent autoanti-i?
Infectious mononucleosis (Epstein-Barr virus) and some lymphoproliferative disorders.
Can autoanti-i cause hemolysis?
High-titer autoanti-i with a broad thermal range can contribute to hemolysis, but significant hemolysis is rare due to weak i expression.
What type of autoanti-i has been linked to HDFN?
IgG autoanti-i.
How are I and i antigens related to the ABH and Lewis antigens?
They are precursors for ABO and Lewis antigen synthesis.
Where are ABH and Ii determinants found on the RBC membrane?
On type 2 chains attached to proteins or lipids.
What defines i antigen activity?
At least two repeating N-acetyllactosamine [Gal(β1-4)GlcNAc(β1-3)] units in a linear form.
What structural change creates I antigen activity?
Branching of i antigen chains.
What gene is responsible for I antigen expression?
IGnT (GCNT2) gene
chromosome of IGnT (GCNT2) gene
chromosome 6 at position 6p24.2
What type of RBCs predominantly carry the i antigen?
Fetal, cord, and i adult RBCs.
What type of RBCs express the I antigen?
Normal adult RBCs, which have more branched structures.
What does the IGnT gene code for?
The branching enzyme that converts i antigen into I antigen.
What inheritance pattern does the i adult phenotype follow?
recessive
What happens when a person inherits I from one parent and i from the other?
They have intermediate I antigen expression.
What causes the i adult phenotype?
Several gene mutations that affect the IGnT gene.
Where, besides RBCs, are I and i antigens found?
On leukocytes and platelets, and possibly on other tissue cells.
In which bodily fluids have I and i antigens been detected?
Plasma, serum, saliva, human milk, amniotic fluid, urine, and ovarian cyst fluid.
Do secreted I and i antigens correlate with their RBC expression?
No, they develop under separate genetic control.
How does the I antigen level in saliva compare between i adult individuals and newborns?
It is quite high, despite their RBCs expressing i antigen.
Who were found to have a cold agglutinin that did not match classical I or i specificity in 1965?
Melanesians
What name was given to the agglutinin that reacted differently with cord, normal adult, and i adult RBCs?
IT (T for “transition”)
how many weeks is IT detected in fetal RBCs
as early as 11–16 weeks
Which two populations commonly exhibited benign IgM anti-IT?
Melanesians
Yanomami Indians of Venezuela.
What diseases have been associated with anti-IT at 37°C?
Warm autoimmune hemolytic anemia
Hodgkin’s disease.
What are some examples of I-related antibodies?
Anti-IA, -IB, -IAB, -IH, -iH, -IP1, -ITP1, -IHLeb, and -iHLeb.
What is a key characteristic of anti-IA?
It reacts with RBCs carrying both I and A, but not with group O, I+, or group A i adult RBCs.
What is a notable property of anti-IH?
It is commonly found in A1 individuals and reacts stronger with group O and A2 RBCs than with A1 RBCs.
What might indicate the presence of anti-IH?
When serum from a group A person agglutinates all group O RBCs but is compatible with most A donor units.
What microorganism is associated with anti-I?
Mycoplasma pneumoniae (linked to cold agglutinin disease).
What disease is linked to anti-i?
Infectious mononucleosis (Epstein-Barr virus).
What conditions are associated with increased i antigen expression on RBCs?
Shortened marrow maturation time or dyserythropoiesis, including:
Acute leukemia
Hypoplastic anemia
Megaloblastic anemia
Sideroblastic anemia
Thalassemia
Sickle cell disease
Paroxysmal nocturnal hemoglobinuria (PNH)
Chronic hemolytic anemia
Does increased i antigen expression always reduce I antigen levels?
No, I antigen can appear normal or even enhanced.
What condition is strongly associated with very high i antigen expression on RBCs?
Chronic dyserythropoietic anemia type II (HEMPAS).
Why are HEMPAS RBCs highly susceptible to lysis by anti-I and anti-i?
Due to increased antibody uptake and greater complement sensitivity.
What congenital condition has been linked to the i adult phenotype in Asians?
Congenital cataracts.
I antigen can be neutralized by what substance
human milk
“I” activity is increased in individuals with what phenotype
Bombay phenotype
T or F:
Anti-I is associated with HDFN
F
anti-i is associated wtih what diseases
infectious monoculeosis
reticuloses
myeloid leukemia
alcoholic cirrhosis
identify the strength of reactivity:
Adult I to Anti-I
strong
identify the strength of reactivity:
Adult I to Anti-i
weak
identify the strength of reactivity:
Adult I to Anti-It
weak
identify the strength of reactivity:
Cord to Anti-I
weak
identify the strength of reactivity:
cord to anti-i
strong
identify the strength of reactivity:
cord to anti-i
strong
identify the strength of reactivity:
cord to Anti-It
strong
identify the strength of reactivity:
Adult i to Anti-I
weak
identify the strength of reactivity:
Adult i to Anti-i
strong
identify the strength of reactivity:
Adult i to Anti-It
weakest
who reported a cold agglutinin in Malanesians that did not demonstrate classical I or i specificity
Curtain and coworkers, 1965
who confirmed the observations of Curtain and coworkers
Booth and colleagues, 1966
