W3 Flashcards
1
Q
Genetics of Rh antigen
A
- RHD and RHCE
- Chromosome 1
- A single haplotype
- Ro: highly prevalent in African ancestry
2
Q
Biochemistry of Rh
A
Protein RhD: present or not (deletion)
Protein RhCE: C/c and E/e
Serves as a structural support for RBC’s wall
RhAG: required for expression of Rh antigens
3
Q
Name scheme
A
- Fisher-Race: 1 gene - 1 product, DCE
- Wiener: 1 gene - 3 products, R1-R2-Ro-Rz and r, r’, r’’, ry
* Ro: prevalent in Black, r is very rare in Asian - Rosenfield: Rh antigen is given a number, Ag’s present –> # positive, Ag’s absent –> # negative
4
Q
Antibody of Rh
A
Ig, unexpected
D: no dosage, CE: dosage
Enhanced by enzyme / Resistant to chemical
Ab persist for years after transfusion or pregnancy
Lead to extravascular hemolysis
Immunogenicity: D>c>E>C>e
5
Q
Ab of D, C/c, E/e
A
- D: most immunogenic, present or absent, weak or partial, no dosage
- C/c: Differ 1 aa, dosage
- E/e: Differ 1 aa, dosage, anti-E is often and go with anti-c
6
Q
Antigen f
A
- Compound antigen
- Present only on cells having c and e in the same haplotype
- Occurs less often than big 5
- Can cause rxn
7
Q
Antigen G
A
- Present on cells having D positive OR C positive
- Important for mom/baby studies
8
Q
Rh Null
A
- Missing RhAG –> Rh gene is not expressed
- Amorph: Gene RhD, RhCE are inactive
- -> True Rh Null show Stomatocytes and mild anemia. They can make anti-Rh29: react with all Rh antigens
- D– : Missing RhCE –> Highest single expression of D. They can make anti-Rh17: react with all from of RhCE proteins
9
Q
RhIg (Rhogam)
A
- Anti-D from human
- Given to Dneg pregnant women at 26-28 weeks & at delivery (trauma, abortion, miscarriage)
- 1 dose negate 30mL whole blood
- Prevent anti-D formation
10
Q
Kell antigen
A
- KEL gene: chromosome 7
- XK gene: X chromosome
- The default: k/Kpb/Jsb
- No KEL gene has multiple mutation (K; Kpa/Kpc; Jsa)
11
Q
Biochemistry of Kell
A
- Only on RBC
- Fetal as early as 10 wks
- Enzymatic activity but unclear
- On RBC wall, Kx antigen is a part of Xk protein which is linked with Kell by a disulfide bond (Km)
- k = Cellano
12
Q
Antibody of Kell
A
- Ag is unimpacted by enzymes
- Ag is destroyed by DTT
- Show dosage technically
- IgG, unexpected
13
Q
Kk antibody
A
- Anti-K: can cause HDFN (lower than anti-D) by suppressing erythropoiesis in baby
- k antigen : 99% pop. has this antigen –> Cellano
14
Q
Kpb/Kpa/Kpc
A
- Kpb: high frequency
- Kpa/Kpc: low frequency
+ Kpa 2% in pp at European ancestry
+ Kpc more rare
15
Q
Jsb/Jsa
A
Jsb: high
Jsa: low - 20% in African ancestry
16
Q
Km and Kx antigen
A
- High frequency
- Kx antigen: on XK protein (encoded by XK gene)
- Km antigen: the di-sulfide bond between XK and Kell protein
17
Q
McLeod Syndrome
A
- Lacking XK protein –> lack Kx antigen and Km antigen
- X-linked condition and exclusive to males
- Result in McLeod Phenotype
- Kell antigen: trace (due to missing Km bond)
- Assoc. with chronic granulomatous dz due to the deletion on part of X chromosome with includes XK and CYBB
18
Q
Null of Kell
A
- Ko: produce anti-Ku
- No assoc. pathology
- Kx antigen increase (as no Kell tail cover), and no Km
- Kell antigen: none
19
Q
MNSs family
A
- Haplotype on chromosome 4
- Ns>Ms>MS>NS
- Total 46 antigens have been described
20
Q
Biochemistry of MNSs
A
- Glycophorin A: M/N - differ 2aa at 1 and 5
- Glycophorin B: S/s - differ 1aa at 29
- Glycophorin B has ‘N’ - assemble structure of N
- Can be used by Plasmodium falciparum
- Expressed on cord cells
21
Q
Antibody of MNSs
A
- Destroyed by enzyme
- Dosage: important (M/N)
- Anti-M and anti-N: IgM (even many cases show IgG), react at cooler temp., insignificant if not react at 37C
- Anti-S and anti-s: IgG, significant and rarer than M/N
22
Q
Anti-M/N antibody
A
- Anti-M: with bacterial infx (can naturally occur), like pH 6.5
- Anti-N: Anti-Nf (after exposure to formaldehyde), common in dialysis patients
- True anti-N rare (due to N on GPB)
23
Q
En(a) - Envelope
A
- Envelop
- On all RBC with M OR N
- En(a)= is M=N= due to GPA deletion
- Unexpected Ab
24
Q
S/s
A
- Significant Ab: IgG, unexpected
- S: 50% pop
- s: 90% pop
- Destroyed by enzyme
25
Q
U (Universal)
A
- U= means S=s=: exclusive in African ancestor
- Anti-U: significant, can cause HTR and HDFN
- Unexpected Ab
- Can make true anti-N
26
Q
MkMk
A
- Complete deletion of GPA and GPB
- Cell: M=N=S=s= –> Null phenotype
- Can make all Ab
- No hematological difference on RBC
27
Q
Mur
A
- GPB mutation common 9% in SE Asia
- 2nd most immunogenic after ABO in some Asian countries –> need routine AbSC test
- Capable of HTR and HDFN
28
Q
Kidd genetics
A
- On chromosome 18
- Jka/Jkb: codominant
29
Q
Biochemistry of Kidds
A
- Express on cord cells
- Urea transporter: Jka=Jkb= increase the lysing time of RBC by 2M urea from 1min to 30min
- Jka/Jkb is located on the 4th extracellular loop of Kidd protein
30
Q
Jka/Jkb
A
- Enhanced results with serum: Ab are better at fixing complement
- Need polyclonal antisera (have both anti-IgG and anti-C3)
- Need to check pt’s history
31
Q
Jk3
A
- Null phenotype: pp missing both Jka and Jkb will make anti-Jk3
- Common in Polynesian population (Hawaii)
32
Q
Duffy genetics
A
- Chromosome 1
- Fya/Fyb: codominant –> destroyed by the enzyme
33
Q
Biochemistry of Duffy
A
- Chemokine receptor: DARC
- Used by Plasmodium vivax to enter RBC
- Found on tissue throughout body
34
Q
Ab of Duffy
A
- IgG, unexpected Ab
- Dosage
- Found on cord cells
- Can cause HTR and HDFN
- Show up with other Ab
35
Q
Ab of Kidd
A
- IgG
- Dosage
- Enhanced by enzyme
- Assoc. with intravascular hemolysis
- Fade in vivo: cause linked delay HTR
- Show up with other Ab –> Honor history
36
Q
GATA box mutation
A
- Found in African ancestry (67%)
- Suppress all Fy antigen on RBC
- Fyb still found on tissue –> Even miss on RBC, no anti-Fyb Ab made.
- Resistant to P. vivax
37
Q
Null of Duffy
A
- Rarer, in European ancestry
- Fya=Fyb= people w/o GATA mutation: make Fy3, Fy5, Fy6 antigen
- Antibody of Fy3,5,6 all react with Fya, Fyb (can’t differentiate)
- Fy3, Fy5: resistant to enzyme (different from Fya/Fyb - destroyed by the enzyme)
- Fy5: absent on Rh Null cells
38
Q
Glob genetics
A
- Two genes: P1PK, P –> interplay makes phenotype
- Make sugar antigen (not proteins as others)
- From Gb2, can make Pk, P (same way) and P1 (another way) antigen - depends on a different mechanism
39
Q
Biochemistry of Glob
A
- Like ABH: composed of sugar
- 5 main phenotypes:
+ P1: P1, P, Pk
+ P2: P, Pk
+ p: None
+ P1k (very rare): P1, Pk
+ P2k (very rare): Pk
40
Q
Ab of Glob
A
- Naturally occuring
- Anti-P1: variable reactivity, IgM, neutralized with P1 substance
- Anti-P: insignificant
- Anti-PP1Pk: Anti-Tja, can seperate out 3 Abs
41
Q
Disease assoc. with Glob
A
- PCH: auto-antiP, Syphilis, after viral infection, biphasic hemolysis,
- Spontaneous abortion: Anti-PP1Pk (placenta’s rich of P antigen –> miscarry early)
- Anti-P1: assoc. with pigeon eggs, liver flukes, hydatid cyst
- P1 receptor: used for Shiga toxin and E. coli
42
Q
Lewis genetics
A
- 2 genes: Lewis, Secretor
- Interplay –> phenotype
43
Q
Biochemistry of Lewis
A
- Sugar –> insignificant
- Type 1 chain
- Not found in fetal cells
- Pregnant women can become Lewis neg temporary
- Secretor gene convert type 1 chain into H chain
- Lewis gene add Fucose to
+ type 1 chain –> Lea
+ H chain –> Leb
44
Q
Ab of Lewis
A
- Can be naturally occurring
- Show up during pregnancy
- IgM
- Neutralized by saliva
45
Q
Lea/Leb antigen
A
- Not antithetical
- No dosage
- Genotype: combination of LE and Secretor gene
+ LE gene: Le (add fucose)/le (not add fucose)
+ Secretor gene: Se (H chain made)/se (only type 1)
46
Q
I biochemistry
A
- Sugar
- i: linear chain vs I: branched chain
- I: not found on cord cells, slowly appear over first 18 months
47
Q
Ab of I
A
- IgM (naturally occurring)
- Enhanced by enzyme
- Auto anti-I: common - found in most adults, can be neutralized by milk (not affect as due to temp.)
- Like cold temp
- Anti-IH: React with compound antigen b/w I and H antigen. Tend to show up in A1 pt
48
Q
Disease assoc. with I
A
- Cold agglutination disease (CAD): due to high titer of auto anti-I
- M. pneumoniae
- Epstein Barr virus
49
Q
Null phenotype of I
A
- ii
- Rare: never develop branched chains
50
Q
Lutheran
A
- Lu(a): low freq, cause mixed field, may be considered as significant
- Lu(b): high freq, significant
- Dominant inhibitor: In(lu) –> suppress Lu gene
- True Null: LuLu –> can make anti-Lu(ab)
51
Q
HTLA (High Titer Low Avidity)
A
- Rxn stay 1+ even dilute or no
- Chido/Rogers: C4d absorbed on RBC, neutralized by plasma
- Bg: Remnant of HLA on RBC, neutralized by chloroquine, Bg(a)/Bg(b)
52
Q
Diego
A
- Anion exchanger
- Di(a)/Di(b)
- Di(a): low freq, found in Native American (esp. South) and Mongolian population.
- Di(b): high freq
- Mom/baby study
- Clinically significant
53
Q
High-frequency Antibody
A
- Mimic warm autos, except not binding to themselves –> A/C: negative
- Special panel
- Check pt’s history
- Perform full antigen typing, look for something odd
54
Q
Low-frequency Antibody
A
- Found by accident: incompatible XM, explained rxn
- Special panel
- Check pt’s history
- Antigen typing is less helpful (as they are low-frequency)
