Mmsc409: Immunohematology I - Exam 3 (100% Accurate)
State the antigens associated with the Lewis blood group system and their frequencies in the population. correct answers The Lewis antigens are Le(a) & Le(b).
-phenotypes possible: Le(a+b-), Le(a-b+), Le(a-b-)
-phenotype frequencies in US population:
Le(a+b-) → 22% white ppl & 23% black ppl
Le(a-b+) → 72% white ppl & 55% black ppl
Le(a-b-) → 6% white ppl & 22% black ppl
Explain the absence of the Le(a+b+) phenotype. correct answers Le(a+b+) is seen in 10-40% of Asian ppl and is very rare in black ppl & white ppl
-occurs due to inheritance of the weak Secretor gene → Se(w)
→the Se gene is typically much stronger than the Le gene in terms of its enzyme fighting for L-
fucose placement on the type 1 precursor chain, so will generally produce more Le(b) than Le(a) - causing increased expression of Le(b) on an individual's RBCs as well = type Le(a-b+)
→a weak Se gene, Se(w), allows for Le(a) secretion and expression to equal that of Le(b), causing a person to type as Le(a+b+)
Explain the interaction of the Lele, Sese, Hh and ABO genes on the production and expression of
the Lewis antigens. correct answers in general:
-if Le gene is present → only Le(a) Ag produced
-if Le gene & Se gene are both present → both Le(a) and Le(b) produced, only Le(b) expressed on RBCs
considering people w/ ABO genes, that also have the Le and Se genes: -Group O: H + Le + Se → Le(b) expression
-Group A: A + H + Le + Se → ALe(b) expression
-Group B: B + H + Le + Se → BLe(b) expression
**typically more Le(a) expression on RBCs of Type O & A1 individuals
State the site of Lewis antigen synthesis. correct answers Lewis antigens are made by tissue cells
& secreted into the body fluid
**one of the reasons they are so unique - most synthesized by RBCs & stay on their surface
→Le antigens can readily be adsorbed onto & eluted back off of RBCs from/to the plasma
Given specific Lele, Sese, Hh and ABO genotypes, determine the substances found in body fluids and the antigens found on the red blood cells. correct answers ABH soluble antigenic substances only present in fluids if they have Se gene Type A w/ Se gene: A & H soluble [antigenic] substances⁃ Type B w/ Se gene: B & H soluble [antigenic] substances⁃ Type O w/ Se gene: only H soluble [antigenic] substances⁃ Type AB w/ Se gene: A, B, & H soluble [antigenic] substances⁃
Explain the phenotype Le(a-b-). correct answers 3 reasons a person can type Le(a-b-): 1. Person has a mutation in the Le gene that causes it to be weak → Le(w) -independent of secretor status b/c neither antigen can be synthesized without Le gene inheritance
-Le(w) will cause decreased production of antigen → might not be detected in secretions
2. Person does not have the Le gene → genotype: lele
3. Pregnant women suppress Le antigen expression, so Ags would not show on phenotyping
-can make anti-Le(a) & anti-Le(b) antibodies also, but typically gone after delivery & return to normal Le type
Describe the characteristics and clinical significance of the Lewis antibodies with regard to hemolytic transfusion reactions (HTR) and hemolytic disease of the fetus and newborn (HDFN). correct answers Cannot cause HDFN & not typically associated w/ HTRs either
-Very rarely reported to be cause of HTR: anti-Lea → fairly common in Le(a-b-)
→Almost never in Le(a-b+)
→IgM - cold-reacting, so can usually ignore unless at 37C & if so, can give cross-matched compatible blood, no need to phenotype
Explain why Lewis antibodies are rarely implicated in hemolytic disease of the fetus and newborn (HDFN). correct answers -Le antibodies are IgM, which canNOT cross the placenta -newborns born Le(a-b-), so don't express any antigens for antibodies of mom too fight anyway
Given antigen and antibody characteristics, determine the specificity of the Lewis blood group antibody. correct answers -Anti-Leb variants → less common than anti-Lea, still IgM & comes in 2 forms:
(1) H-dependent = Anti-LebH:
→Reacts best when both Leb and H are on RBC - Group O or A2 with Le(a-b+) have large amounts of H on RBCs, so react strongly
→Might produce false negatives if tried to use for phenotyping b/c wouldn't react to B or A1 red cells due to lack of H presence
(2) H-independent = Anti-LebL: reacts against all Leb+ red cells, regardless of amount of H → so, best Leb Ab to use for phenotyping RBCs
Explain why people of the Le(a-b+) genotype do not produce anti-Lea. correct answers Le(a-b+) typed people still produce Le(a) antigens, they are just expressed in smaller amounts than Le(b) on RBCs
-mostly found in secretions
State the alleles & antigens associated with the Duffy blood group system. correct answers Duffy
BG = 3 allele system, all of which are co-dominant on chromosome 1 1. Fy(a) - codes for production of Fy(a) antigen
→Fy(a) Ag frequency: 65%
2. Fy(b) - codes for production of Fy(b) antigen
→Fy(b) Ag frequency: 80%
3. Fy - does not code for antigen production, null genotype: FyFy
→more common in black population
→can also be heterozygous -ex: phenotype Fy(a+b-) could be due to genotype Fy(a)Fy
Identify the Duffy phenotypes and their frequencies in the US population. correct answers 1. Fy(a+b-) → 17% of white ppl, 9% of black ppl, 90.8% of Chinese ppl
2. Fy(a+b+) → 49% of white ppl, 1% of black ppl, 8.9% of Chinese ppl
3. Fy(a-b+) → 34% of white ppl, 22% of black ppl, 0.3% of Chinese ppl
4. Fy(a-b-) → v rare in white ppl, 68% of black ppl, 0% of Chinese ppl
Explain the importance of the Fy(a-b-) phenotype in the black population. correct answers Fy(a-
b-) RBCs resist infection to Plasmodium vivax (P. vivax) - organism causes malaria in humans
→Attachment of merozoite to RBC can happen regardless of Duffy Ag status - invasion cannot happen without Duffy Ag
-In black population: a variant of Fy(b) gene can cause Fy(a-b-) phenotype to occur → Fy(b) antigen not expressed on RBCs, but can be expressed in other tissues
Explain the effect of enzymes on the Duffy antigens and the significance of this effect in antibody identification. correct answers Duffy antigens destroyed by enzymes (ficin, papain, bromelyn) and ZZAP
→ZZAP: 0.2M DTT (dithiothreitol - reduces disulfide bonds), papain, PBS -Useful for antibody identification in patients with multiple antibodies
Discuss the characteristics and clinical significance of Duffy antibodies. correct answers Duffy antigens: only moderate immunogens, well developed at birth
→Anti-Fya found 3x less frequently than anti-K & Anti-Fyb found 20x less frequently than anti-
Fya
→Usually IgG antibodies - rarely bind complement, react best at 37C & AHG
-Both Abs associated with transfusion reactions & HDFN
-Provide Ag neg blood if current or hx of Ab
Explain the absence of both anti-Fya and anti-Fyb in the black population with the phenotype Fy(a-b-). correct answers →anti-Fy(a)
→anti-Fy(b) rarely seen b/c 68% of population has Fy(b) gene variant, leading to Fy(a-b-) phenotype that causes Fy(b) to not be expressed on RBCs -Fy(b) in these cases can still be expressed in other tissues, so pt has the Ag it just doesn't appear when typing
Given antigen and antibody characteristics, determine the specificity of the Duffy blood group antibody. correct answers Duffy blood group antibodies may exhibit dosage
→can be autoantibodies that mimic specificity
-Other Fy antigens: Fy3, Fy4, Fy5, Fy6
→Antibodies to these four are rarely encountered
-Fy(x): weak expression of Fy(b) antigen
Explain the importance of transfusing antigen negative blood when Duffy blood group system antibodies are identified in a patient's specimen. correct answers important that Duffy antigens not present in donor blood to a patient w/ Duffy antibodies b/c these Abs are associated with
