Uncommon Blood Group Flashcards
play a major role in ore-transfusion testing outcomes
ABO and Rh
More than ____ unique antigens belonging to additional blood group systems exist out there have been identified
300 unique antigens
Antigenic exposure usually occurs in
Pregnancy or Blood Transfusions
8 Major Blood Group System
Kell, Duffy, Lutheran, Lewis, I, P, MNSs, Kidd
11 Minor Blood Group Systems
XG, Scianna, Dombrock, Cartwright, Chido-Rodgers, Colton, Knops, Indian, Gerbich, BG, Diego
When and who discovered MNSs Blood Group
Discovered by Landsteiner and Levine in 1927 when immunizing rabbits
MNSs Blood Group ISBT #
002
MNSs Blood Group is Composed of more than ____ antigens, with the most common: ___
40 antigens, most common: M, N, S, s, and U
Lectins used for MN typing:
Anti-M- Iberis amara
Anti-N- Vicia graminea, Bauhinia variegata, Bauhinia purpura
MNSs genes are traced at?
chromosome 4q28-q31
what gene codes for glycophorin A
GYPA gene
what gene codes for Glycophorin B
GYPB gene
Considered to be the ancestral gene
GYPA gene
how many exons does the gypa ang gypb genes have
gypa - 7 exons
gypb - 5 exons and one noncoding (pseudoexon)
similarities between gypa and gypbd
- Alleles for GYPA and GYPB are codominant
- Both are highly homologous
antigens that are fully developed at birth
MNSs Antigens
M (MNS1) & N(MNS2) antigens reside in the
in the Glycophorin A of the RBC membrane
Biochemically, MNSs antigens are attached to the glycophorin proteins - These proteins are
Sialic acid-rich glycoproteins, therefore called “Sialoglycoproteins”
M and N are at the ____ of GPA
extreme terminus
GPA and GPB are also expressed in??
renal endothelium and epithelium
N antigen is defined by __ and ___
Leucine and Glutamic acid
M antigen is defined by
defined bv Serine and Glycine
how many copies of GPA is there per RBC
200, 000 to 1, 000, 000 copies
S (MNS3), s (MNS4) antigens is discovered in __ by __
Discovered in 1947 by Walsh and Carmel Montgomery
The s antigen (antithetical partner of S) was discovered in?
1951
S (MNS3), s (MNS4) antigens can be found in ___ on RBC membrane
Glycophorin B
S antigen is defined by ___
methionine
s antigen is defined by
threonine
how many copies of GPB is there per RBC
50, 000 to 250, 000 copies
U (MNS5) antigens can be found in ___ on RBC membrane
Glycophorin B
is a “Universal” antigen. This makes it a high incidence antigen
U (MNS5) antigens
where can u antigens be found among individuals
Found on RBCs of all individuals except about 1% of African Americans (1-35% Africans)
U (MNS5) antigens was discovered by ___ via ___ in ___
Weiner via anti-U in 1953
RBCs with U antigen also carries what antigen?
S and s antigens
is one or more antigens produced by alleles at a single gene locus or at loci so closely linked that
crossing over does not occur or is very rare
blood group system
where can MNSs Blood Group (ISBT # 002) be found
Found on RBCs and some fissues but NOT in secretions
MNSs Blood Group (ISBT # 002) is used for what test?
paternity testing
M and N are easily destroyed by what enzymes
(Ficin, Papain, Bromelin, Trypsin, and Pronasel
are less easily destroyed by enzymes
S and s
Ficin, Papain, Bromelin, Pronase and Chymotrypsin can destroy s and s activity but the amount of degradation may depend on the?
strength of the enzyme solution, length of treatment, and enzyme-to-cell ratio
enzymes that cannot destroy S and s
Trypsin, Dithiothreitol, Glycine-acid EDTA
a term used to describe a pair (and occasionally more than a pair) of antigens that are coded by different alleles of a single gene
Antithetical
M antigen frequency in whites and blacks
whites - 78%
blacks - 74%
N+ antigen frequencies in whites and blacks
whites 72%
blacks 75%
S+ antigen frequencies in whites and blacks
whites - 55%
blacks - 31%
s+ antigen frequencies in whites and blacks
whites - 89%
black - 93%
U+ antigen frequencies in whites and blacks
whites: 99.90%
blacks: 99%
rarely natural (formed due to transfusion or pregnancy)
IgM
What are the characteristics of Anti-M and Anti-N antibodies?
• IgM (rarely natural, can form due to transfusion or pregnancy)
• Cold-reactive saline agglutinins (best at 4°C)
• Do not bind complement (do not cause HDFN or HTR)
• Reaction enhanced by acidification
What are the unique features of Anti-M?
• Reaction enhanced at pH 6.5
• Common in multiparous women
• Observed in children and bacterial infections
• Can demonstrate dosage
What are the unique features of Anti-N?
• Less common than Anti-M
• Specific at alkaline pH
• Some are IgG
• Can demonstrate dosage (reacts better with M−N+ than M+N+)
• Observed in renal patients using formalin-sterilized dialysis machines
What are the characteristics of Anti-S and Anti-s?
• IgG, reactive in AHG phase
• Reacts at 37°C (some between 10°C–22°C)
• Binds complement, can cause HDFN and HTR with hemoglobinuria
• May exhibit dosage effect
What are the characteristics of Anti-U?
• IgG, enhanced with enzyme treatment
• Reacts at 37°C and AHG phase
• Can cause HDFN and HTR
• Associated with decreased red cell survival
How do MNSs autoantibodies develop?
• Some individuals have altered glycophorin A (GPA)
• Their antibodies target the missing portion of the common antigen
How was the Lutheran (Lu) blood group discovered
Discovered in 1945 in a Lupus erythematosus patient
Anti-Lua was named after the donor ___
“Lutheran” (originally “Lutteran” but mislabeled)
was discovered in __ as the antithetical partner to Lua
Anti-Lub 1956
anti M is commonly seen in?
multiparous women, children and bacterial infections
ISBT #005
LUTHERAN BLOOD GROUP - “Lu”
How many antigens are in the Lutheran system?
20 antigens
When are Lutheran antigens detected on fetal RBCs?
As early as 10-12 weeks of gestation
How well developed are Lutheran antigens at birth?
Poorly developed
On which tissues, besides RBCs, are Lutheran antigens found?
Brain, lungs, pancreas, placenta, skeletal muscle, and hepatocytes
Which enzymes destroy Lutheran antigens?
Trypsin and alpha-chymotrypsin
Which enzymes do NOT destroy Lutheran antigens?
Ficin, papain, glycine-acid EDTA
What type of protein are Lutheran antigens located on?
Type 1 transmembrane protein
How many forms of Lutheran glycoproteins exist?
Two (due to alternative RNA splicing)
Describe the Longer Lu glycoprotein.
• 85 kD protein
• 597 amino acids
• 19 amino acid hydrophobic transmembrane domain
• Cytoplasmic domain with 59 amino acids
Describe the Shorter basal cell adhesion molecule.
• 78 kD protein
• Shorter cytoplasmic domain
• External portion has five disulfide-bonded domains
To which superfamily do Lutheran glycoproteins belong?
Immunoglobulin superfamily
What is the function of Lutheran antigens?
Linked to adhesion properties and intracellular signaling
What is the significance of Lutheran antigen presence in the placenta?
Contributes to decreased likelihood of HDFN via adsorption
On which chromosome is the Lu gene located?
Chromosome 19q13.2
Which other blood group gene is linked to the Lu gene?
Secretor (Se) gene
What immunoglobulin class is Anti-Lua?
IgM
How does Anti-Lua react?
• Naturally occurring saline agglutinin
• Reacts at room temperature
• Some can bind complement
Can Anti-Lua cause hemolytic transfusion reactions (HTRs)?
Yes, but usually delayed HTRs
What immunoglobulin class is Anti-Lub?
Usually IgG
How does Anti-Lub react?
Reacts at 37°C and AHG phase
Can Anti-Lub cause hemolytic disease of the fetus and newborn (HDFN)?
Rare, but possible
anti lub is stimulated by?
pregnancy or transfusion
What type of immunoglobulin is Anti-Lu3?
IgG
What makes Anti-Lu3 unique?
It reacts with all RBCs except Lu(a-b-) RBCs
What type of immunoglobulin is Anti-Lua?
IgM
How does Anti-Lua react?
• Naturally occurring saline agglutinin
• Reacts at room temperature
• Can cause delayed hemolytic transfusion reactions (HTRs)
What type of immunoglobulin is Anti-Lub?
IgG
How does Anti-Lub react?
• Reacts at 37°C & AHG phase
• Stimulated by pregnancy or transfusion
• Can cause delayed HTRs
When and how was the XG blood group discovered?
In 1962, from the serum of a multiply transfused man
What was the first XG antigen discovered?
Xga
Why does Xga antigen have a higher prevalence in females?
It is controlled by an X-linked gene
How did the XG blood group get its name?
• “X” for the X chromosome
• “G” for Grand Rapids, where the patient was treated
Where is the XG gene located?
Xp22.3 on the X chromosome
Which gene codes for CD99?
MIC2, located at Xp22.2
Why was CD99 included in the XG system?
MIC2 and XG genes are adjacent and homologous
How does the Xga glycoprotein interact with the RBC membrane?
It crosses the RBC membrane once
What is the prevalence of Xga in men vs. women?
• 66% in men
• 89% in women
Why do women have a higher prevalence of Xga?
Women have two X chromosomes, so they can be homozygous or heterozygous
Why was CD99 added to the XG system?
It is genetically adjacent to the XG gene and shares homology
What immunoglobulin type are XG antibodies?
IgG
Are XG antibodies naturally occurring?
Yes
Do XG antibodies cause HDFN or HTRs?
No
Lua and Lub are produced by
allelic codominant genes
