Rh antigen Flashcards
1
Q
What is the second autosomal linkage in humans?
A
Rh blood group and gene for elliptocytosis
2
Q
What was the Fisher and Race theory?
A
3 closely linked genes Inherited has a haplotype Crossover was rare 1 gene = 1 antigen Did not explain all the low freq
3
Q
What was the Weiner theory?
A
1 gene codes for 1 agglutinogen that has 3 factors
Each factor represented an antigen
Thought that R and r could code for unlimited factors
4
Q
What is the ISBT number for Rh?
A
004
5
Q
What was Tippetts theory?
A
Correctly described the 2 gene inheritance
1 RHD gene and 1 RHCE gene
6
Q
What antigen does ISBT 4.6 code for?
A
f
7
Q
What antigen does ISBT 4.7 code for?
A
Ce
8
Q
What antigen does ISBT 4.8 codes for?
A
Cw
9
Q
Most prevalent Rh phenotypes in whites?
A
R1 (42%) > r (37%) > R2 (14%) > Ro (4%)
68% of whites are C +
80% are c+
10
Q
Most prevalent Rh phenotypes in Blacks?
A
Ro (44%) > r (26%) > R1 (17%) > R2 (11%)
27% are C+
98% are c+
11
Q
Characteristics of Rh antibodies
A
IgG; rarely IgM
Do not activate complement
- Causes extravascular hemolysis
Enhanced by enzymes
12
Q
Rh most to lease immunogenicity
A
D > c > E > C > e
13
Q
What is anti-RH17?
A
RH17 = Hro (High freq)
antibody that reacts with all cells except D– and D**
Auto antibody is known as anti-pdl (partial deleted)
14
Q
What is anti-RH29?
A
RH29 = total Rh
antibody that reacts with all cells except Rh null cells
Immune stimulated in Rh null
Some anti-RH29 reacts with Rh mod cells
auto antibody is known as anti-dl (total deleted)
15
Q
What are anti-hr(s) and anti-hr(b)?
A
antibody reacts with all cells but can look anti-e reacting with stronger with e+ cells. Made by people with variant e. Seen in black population.
16
Q
What is anti-LW?
A
Antibody reacts stronger with D+ cells than D- cells
- May need to enhance to show reactivity with D- cell
Negative with Rh null cells
Anti-LW reacts with all cords regardless of Rh type
DTT destroys
Seen as an auto antibody with no clinical significance
17
Q
Cw
A
Found with multiple antibodies
Cw is found in 2% of whites
18
Q
Goa
A
Goa (RH30) is present in DIVa partial D cells
present in 2% of blacks
19
Q
V antigen is historically known as
A
ce^s
RH10
occurs in 30% of blacks
20
Q
The VS antigen is historically known as
A
e^s
RH20
occurs in 32% of blacks
21
Q
What is anti-Evans antibody?
A
Evans antigen is present on D** cells and not D– cells
22
Q
What is anti-f?
A
f is present with c and e are in cis
present on Ro and r cells
Appears to be anti-c and -e, but only reacts to shared determinate on Ro and r cells
23
Q
What is anti-G?
A
reacts with all cells carrying D or C or both
Transfuse D- C- blood
Differentiate in pregnant females for RHIG
24
Q
What amino acid change makes G antigen?
A
Serine at position at 103 on RHD and RHCE gene
25
Anti-Ce
Also called RH7 or rhi
Similar to f, reacts with Ce+ cells in cis (R1 or r')
Most anti-C is Ce in Rh positive people
Ce is present in 68% of White and 27% of blacks
- Most C+ will be e+
26
What disease show reduced expression of Rh antigens
```
Hereditary spherocytyosis
Leukemias
Myeloid metaplasia
Myelofibrosis
Polycythemia
```
27
What causes anemia in Rh null or Rh mod people
RHag is required for strong cytoskeleton of RBC
Integrity of membrane is compromised
Increased osmotic fragility - abn cation fluxes
Stomatocytes present
28
What chromosome is RHD and RHCE located on?
Chromosome 1
29
Characteristics of RHD and RHCE genes?
Both are 416 amino acids long with 10 exons
92-97% identical
genes run in opposite direction = "hair pin" formation and genetic recombination
30
What chromosome is RHAG located on?
Chromosome 6
31
What chromosome is LW located on?
Chromosome 19
32
What cells have the most D antigens present?
D--
D**
R2R2
33
What is the amino acid that determines C
Serine at 103
Ser103Pro
34
What is the amino acid that determines c
Proline at 103
Ser103Pro
35
What is the amino acid that determines E
Proline at 226
Pro226Ala
36
What is the amino acid that determines e
Alanine at 226
Pro226Ala
37
What is the Rh box?
RHD gene is flanked by 2 Rh boxes
Identity boxes
In whites, Deletion of D gene occurs in RH boxes
38
What is the structure of D antigen?
```
Pass membrane 12x
Has a C and N terminus in cytoplasma of cell
Non-glycosylated = Hydrophobic
Non=phosphorlated
More than 30 epitopes
```
39
What is X1r?
Normal RHAG gene
Makes precursor substance 2 from precursor 1
Must be present to make RH and LW antigens
40
What is Xor?
No RHAG gene
= Rh null regulator
No Rh antigens or LW antigens
41
What is Xqr?
Rh mod phenotype
| RHAG makes a modified precursor substance 2. DCE and LW antigens are present but weak
42
What is rr (double bar)
Amorph Rh null
No DCE or LW antigens
RHAG is normal
D deletion with homozygous inactive RHCE genes
43
High protein Anti-D
Human source = Polyclonal
20-24% protein added to enhance IS of IgG antibody by bringing RBC's close together
May see spontaneous agglutination with warm auto
44
IgM Saline anti-D
Human source
| Expensive because hard to find donors with IgM Anti-D
45
Chemically modified anti-D
Human source
| DTT breaks the disulfide bonds in the hinge region to allow IgG to crosslink 2 RBC's
46
Monoclonal anti-D
Combonations of IgM and IgG
Can be monoclonal IgM with human IgG
or both monoclonal IgG and IgM
47
What is crawford antigen (ceCF)?
RH43 - Found in Africans 0.1%
amino acid substitution in the RHCE gene that results in a D like epitope
D gene is NOT present.
Negative at IS but reacts at AHG phase
48
What causes a false positive with anti-D?
Warm or Cold auto antibodies
Rouleaux or spontaneous red cells agglutination
contaminated reagent
Polyagglutination - seen with ortho (human source)
49
What causes a false negative with anti-D?
Failure to add reagent
RBC suspension too heavy
Shaking tube to hard
Red cells with positive strong DAT (seen in HDFN)
50
How many D antigen sites are on most normal D+ cells?
10-33,000
51
How many D antigen sites are on D-- or D** cells?
75-300,000
52
How many antigens are on Weak D cells?
<100-10,000
53
How many antigens are on Del cells?
>20
54
% of Whites and Blacks that D+?
85% of whites
| 92% of blacks
55
% of Asians and Native Americans that are D+?
99%
56
What causes D neg in most Caucasians?
D gene is deleted
| Chromosome misalignment and unequal crossing over between the Rh boxes
57
What is the pseudogene?
Occurs in African populations (66% of Rh-)
There is a premature stop codon which does not allow the D gene to be expressed
D gene is present but inactive
58
What is the Del phenotype?
Amino acid change that results in very low D antigens on RBC
Will type D- at IS and AHG phase
Must adsorb and elute to detect D antigen
Found in 10-30% Asians
Exon 9, inside the membrane, is deleted
Most are C+ (Rh negative)
59
Weak D
```
Quantitative = Less D antigen present
Amino acid change occurs inside the membrane
May need AHG to detect
All D epitopes are present
Types 1-3 will not make anti-D
```
60
Partial D
```
Qualitative
Missing some D epitopes
Many will react as IS
Most due to hybrid gene with RHCE gene
Amino acid change on external loops of D antigen
Can make allo-anti-D to missing epitopes
Many assoc. with low frequency antigens
```
61
C in Trans to D
Occurs in Ror'
Steric arrangement if C and D interferes with D expression
D antigen is normal = Can rec'v D+ cells
62
What is Ceppellini effect?
D is weaker in Presence of C
| R1 is weaker than R2 cells
63
Partial DVI
Found in Whites 0.02-0.05%
Accounts for 6-10% of all partial D's that make anti-D
BARC+ (RH52; low freq)
Not detected at IS but variably positive in AHG.
FDA Requires that monoclonal anti-D NOT detect DVI at IS, so females are typed as D neg
64
DVII
Found in Whites
| Tar+ (RH40; Low freq)
65
DIVa
Found in blacks
Goa+ (RH 30; Low freq)
GoDIVa
66
DIIIa
```
Found in Blacks
Assoc. with Variant RHCE*ce^s
Make anti-D, anti-c, or anti-hr^b
DAK+ (RH54; Low freq)
Consistently strong D epitopes - types D+
```
67
What partial D's will type D positive?
III, IV, VII
| 3 + 4 = 7
68
D**
Has D, G, RH29 (total Rh) + RH37 (EVANS)
Has less D antigen than other D deletions
Can make anti-Rh17 and anti-RH47 (DAV
69
D--
Has D, G, and RH29 Total
D gene is present and homozygous for RHCE null
Most D antigen present
Form anti-e or Ce (Rh 7)
Also, make anti-Rh17 or anti-Hr = Reacts with all common Rh phenotypes
70
RHD*DHAR
Formerly called RoHAR but better named ceHAR
Found in 0.01% Germans
FPTT+ and RH33
Hybrid CE-D-CE gene = No D antigen; Only one D epitope insertion
R HAR = Normal c, reduced e, f, Hro and D = (D)c(e)
Most IgM reagents detect; can make anti-D
71
What is Rh null regulator?
NO RHAG protein due to inactivating mutations
Xor
NO DCE, LW, GPB (S, s, U) or FY5 antigens
Reduced CD47
Make anti=RH29 (total Rh)
72
What is Rh mod?
XQr = RHAG is modified and not expressed normally
Rh antigens are present but weakend
Must adsorb and elute to detect Rh antigens
73
What is Rh null amorph?
rr (double bar)
amorph from deleted D gene and homozygous for RHCE containing inactivating mutations
Normal RHAG but no DCE, LW. Normal Ss and weak U
Rare, occurs in whites
74
Frequency of Rh null
One in 6,000,000
75
Can an Rh Null pass Rh gene to child?
rr and Rh null (R1R1) person can pass one normal RHAG and R1r to child = Rh positive from 2 Rh neg parents
76
What does the FDA require for weak D on instrument?
Instrument must detect a weak D of 1+ or greater.
| Weaker than 1+ will be labeled as Rh negative
77
What does the RHAG code for?
RH-associated glycoprotein
| It carries 4 antigens and Rh core complex
78
What is Rh core complex?
Interacts with Band 3, GPA, GPB, LW, and CD47 and is associated with the membrane skeleton via Ankyrin and Protein 4.2
79
What is CD47?
Part of Ig superfamily
Generates a "survival signal"
-Anti-CD47 drug
80
What is RHAG1?
Duclos Antigen
High incidence
Absent Rh null regulator and Rh mod phenotype
81
What is RHAG2?
OIa antigen
| Low frequency
82
What is RHAG3?
DSLK antigen
Stands for Duclos like antigen
Reacts like Duclos but proven unique
83
What is RHAG4?
Low freqency
Only one case and caused HDFN
Person was African
84
What is f antigen?
RH6
Anti-f reacts with c in cis to e or Ro and r cells
65% of Caucasians
92% of Blacks - R0 and r very common
85
What is Ce antigen?
RH7 also known as rhi
most immune anti-C is in Rh positive is really anti-Ce
antibody reacts to C and e in cis position or R1 and r' cells
68% of whites - R1 is most common
27% of blacks
86
What is Cw antigen?
```
RH8
weak C
W stands for Willis
Low freq present in 2% of whites, 1% of blacks, 4% finns, and 9% latvans
Antithetical to Cx and Mars
Most Cw cells are C+
```
87
What is Cx antigen?
RH9
Weak C
Very low frequency 0.01% (seen in 1.8% Finns)
Antithetical to Cw
88
What is RH39?
C-Like
Antibody reacts stronger C+ cells than C-
Antibody can be absorbed by C+ and C- cells except Rh null cells
89
What is RH51?
MAR antigen
High prevalence to Cw and Cx
100% are positive except 0.2% of Finns are MAR neg
90
What is RH2?
C antigen 4.2
Partial C = Cw, Cx, D(C)(e) and (C)ce^s
Anti-C in blacks may be anti-hrB (RH31)
68% Whites and 27% of blacks C +
91
What is RH3?
E antigen 4.3
Some examples of Anti-E are naturally occurring
29% of Whites and 22% of Blacks E+
92
What is R11?
Ew
Partial antigen detected by some but not all anti-E reagents
0.01% (Germany)
93
What is RH4?
c antigen 4.4
Most clinically sig next to D antigen
80% of Whites and 98% of blacks are c+
94
What is RH26?
c like antibody
antibody reacted with some c+ but not all cells
c+ RH26- cells found in Italians and Dutch
95
What is RH5
e antigen 4.5
Antigen for e has many parts - not full understood
Allo anti-e seen in e variants (missing e epitopes)
96
What are the two categories of partial e?
Partial e that make anti-e like antibody
| Partial e and partial Hro (RH17) that make antibody that reacts with cells except Rh null
97
What is hr^s?
```
RH19
Present in 98%
R2R2 cells are negative
Negative seen in Africans (1% of Bantus)
make anti-Hr
Appears to be anti-e in e positive people
```
98
What is hr^b?
RH31
High frequency
Anti-e antibody in e positive person
Weak anti-hr^b may look like anti-C in blacks. Reacts stronger with C+ cells
Anti-hr^s and anti-hr^b are found in DIII people
Common in sickle cell patients
99
What is V?
RH10
ce^s
c is cis to e^s
30% of blacks are postitive
100
What is VS?
```
RH20
e^s
Found in 32% of blacks
Most V+ are VS+
hr^b neg cells are VS+
```
101
What is the rG haplotype>
rG cells have not DCE antigens but G is present
| Assoc with JAHK
102
What is RH18?
Hr antigen
| High freq present on all except RHCE null, Rh null and Hrs negative
103
What are the high prevalent Rh antigens?
Hr^o, Hr, hr^s, RH29 (total), hr^B, Hr^b, NOU, SEC, DAV, MAR
104
What are the low prevalent Rh antigens?
Dw, Goa, RH32, RH33 (DHAR), TAR, FPTT, BARC, DAK, Crawford
105
What is LW5?
LWa - 97%
106
What is LW6?
LWab - 3%
107
What is LW7?
LWb - Rare
108
What causes LW(a-b-) phenotype?
Rh null will type as LW(a-b-) even if LW gene is present
109
What is the function of LW antigen?
It's an Intercellular adhesion molecule (ICAM)
maker for lymphocyte maturation and differentiation
May help stabilize the erythroblastic islands
Involved in removal of old RBC's
110
How do you differentiate anti-D and anti-LW?
LW will react with all cord cells regardless of D type
LW is destroyed by DTT and pronase
Both are resistant to Ficin/papain
111
How do you transfuse a person with Anti-LW?
D neg RBC have less LW and survive well
112
What subclass is Anti-D most commonly?
IgG1 and IgG3
113
What does a weak anti-hrb resemble?
Anti-hrb will react stronger with C+ cells so may appear to be anti-C. May also appear as anti-Ce Occurs in black population.
114
How do you identify anti-hrs?
e like antibody in e+ people
| To correctly identify anti-hrs, you must have cells that are cells that are e+ hrs-.
115
DFR
Type of partial D that is positive for FPTT (RH50)
116
DBT
Type of D-CE hybrid that is found in blacks
R^N (RH32) +
Normal D with weak C and e
Can make anti-SEC (RH46; high freq)
117
What partial/weak D's will be detected?
III, IV, VII will type as D+ (3+4=7)
Variable results with DVI, DBT, DHAR, and Crawford
DVI will type neg at IS per FDA requirements
