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Rh BLOOD GROUP SYSTEM. AHLS 311. HISTORY. Ab in serum of mother of stillborn child; responsible for the death of fetus? (1939, Levine and Stetson) Rb-derived Ab to Rhesus monkey RBCs reacts with 85% of human subjects; same Ab as reported by Levine? (1940, Landsteiner and Weiner) - PowerPoint PPT Presentation
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Rh BLOOD GROUP SYSTEMRh BLOOD GROUP SYSTEM
AHLS 311
HISTORYHISTORY
Ab in serum of mother of stillborn child; responsible for the death of fetus? (1939, Levine and Stetson)
Rb-derived Ab to Rhesus monkey RBCs reacts with 85% of human subjects; same Ab as reported by Levine? (1940, Landsteiner and Weiner)
Erythroblastosis fetalis (HDN) linked with Anti-
Rh (1941, Levine et al)
NOMENCLATURE: NOMENCLATURE: 4 VERSIONS4 VERSIONS
Fisher Race Suggested 3 sets of closely linked alleles (D
and d, C and c, E and e) Each gene (except d, which is an amorph)
causes production of an Ag Inherited from parents in linked fashion as
haplotypes See Tables 6-1 and 6-2
NOMENCLATURENOMENCLATURE
Weiner Multiple alleles at 1 complex locus 1 locus encodes for production of an
agglutinogen which has 3 factors (antigens or epitopes)
Abs can recognize single or multiple factors See Table 6-3
WEINER’S THEORYWEINER’S THEORY
WEINER & FISHER-RACE WEINER & FISHER-RACE TERMINOLOGYTERMINOLOGY
WEINER & FISHER-RACE WEINER & FISHER-RACE TERMINOLOGYTERMINOLOGY
1 ( C)
D C
2 ( E )
D c E
0 (neither C or E )
D c e
Z (both C & E )
D C E
‘( C)
d C e
‘’ ( E )
d cE
(neither C or E )
d c e
y (both C & E )
d C E
D = R
d = r
NOMENCLATURENOMENCLATURE
Rosenfield No genetic assumptions made Numerical system
If listed alone, the Ag is present (Rh:1 = D Ag)
If listed with a “-”, the Ag is not present (Rh:1, -2, 3 = DcE)
If not listed, the Ag status was not determined
Adapts well to computer entry
COMMON Rh TYPES BY COMMON Rh TYPES BY 3 NOMENCLATURES3 NOMENCLATURES
NOMENCLATURENOMENCLATURE
Internatl. Soc. of Blood Transfusion 6 digit number for each Ag specificity First 3 indicate the blood group, eg., 004 =
Rh Last 3 indicates the Ag specificity, eg.,
004001 = D Ag of Rh system For recording of phenotypes, the system
adopts the Rosenfield approach
Rh PHENOTYPINGRh PHENOTYPING Uses
Parentage testing Predicting hemolytic disease of the newborn
(HDN) Confirmation of Rh Ab specificity Locating compatible blood for recipients
with Rh Abs Protocol
Mix unknown RBCs with Rh antisera Take tubes through phases (IS,
heat/potentiator, AHG, CCC); record data Use published frequencies and subject
information to determine genotype
Rh GENOTYPING PHENOTYPING DATA Reactions with Anti-:
POSSIBLE GENOTYPES
D C E c e 1st CHOICE
2ND
CHOICE + + - - +
- - - + +
+ + - + +
+ + + + +
GENOTYPE GENOTYPE FREQUENCIESFREQUENCIES
Dce (R1) 0.42 dce (r) 0.37 DcE (R2) 0.14 Dce (R0) 0.04 dCe (r’) 0.02 dce (r”) 0.01 DCE (Rz) <0.01 dCE(ry) <0.01
The probability of 2 frequencies appearing together = the product of those 2 frequencies. For example, DCe/dce occurs with a frequency of 0.42 X 0.37 or 0.155.
Rh ANTIGENSRh ANTIGENS
Nonglycosylated proteins (A,B,H are CHOs) Transmembrane molecules D and CE are epitopes of proteins with 417 Aas
that traverse the membrane 12 X DNA sequences of D and CE differ by only 44
base pairs; CE, Ce, cd and cE are even more similar to D
Integral part of RBC membrane (Rhnull people have mild hemolytic anemia)
Density of Rh Ags on RBCs varies by phenotype (see Table 6-7)
MODEL OF Rh PROTEINMODEL OF Rh PROTEIN
D ANTIGEN VARIATIONSD ANTIGEN VARIATIONS Weak D
Some cells require addition of AHG (IDAT) to demonstrate agglutination with Anti-D
3 mechanisms causing weak D expression Genetic - inheritance of D genes which
result in lowered densities of D Ags on RBC membranes
C trans - position effect; the D gene is in trans to the C gene, eg., Dce/dCe (C and D Ag arrangement causes steric hindrance weakening D expression)
D mosaic - 1 or more parts of the D Ag is missing; may result in production of Anti-D
People with weak D are considered Rh+ and receive Rh+ blood (except mosaics)
D ANTIGEN VARIATIONSD ANTIGEN VARIATIONS
Enhanced D When c and D are in double doses, eg.,
cDe/cDe, (C has limiting effect on expression of D)
D-- or D .. represent partial locus deletions; usually seen in consanguinous situations
D TESTINGD TESTING Anti-D reagents
Saline-based - Low protein (fewer false positives); long incubation times; cannot convert to weak D testing
Protein-based - Faster, increased frequency of false positives; requires use of Rh control tube, converts to weak D testing
Chemically modified - “Relaxed” form of Anti-D in low protein medium; few false positives; saline control performed; converts to weak D testing
Blends of mAbs
D TESTINGD TESTING Protocol
Add Anti-D to “D” tube; Rh control to “C” tube Spin, read and record
If “D” is positive, cells are Rh positive If “D” is negative, continue testing
Add 22% albumin and incubate for 20” at 37oC Spin, read, and record Wash 3 X in saline Add AHG, spin, read, and record If “D” is positive after heat/albumin or AHG
cells are weak D positive; if negative, cells are Rh negative; “C” should always be negative
Add check cells to neg. tubes; spin, read & record
WEAK D Ag IN THE LABWEAK D Ag IN THE LAB Differences from normal D expression
Quantitative (inherited weak D or position effects)
Qualitative (mosaic D; could produce Anti-D) If cells are weak D, consider the person to be Rh +
Dw not given to D negative recipients D positives usually OK for Dw recipients Dw mothers do not receive RhoGAM
Donors and expectant mothers should be tested for weak D; transfusion recipiencts +/- for weak D testing (Dw people may receive D negative blood)
OTHER ALLELES AND OTHER ALLELES AND ANTIGENSANTIGENS
Weak C (Cw) Not allelic to C and c (C and Cw usually seen
together) 2% of whites; very rare in blacks Anti-Cw may be naturally occurring and
shows dosage f (ce)
When c & e are in cis, eg., dce/DCe Combination Ag Anti-f may be helpful in phenotyping
OTHER ALLELES AND OTHER ALLELES AND ANTIGENSANTIGENS
Ce When C and e in cis Compound Ag Ab helpful in phenotyping
G Always found with C-positive RBCs; usually
with D-positive cells Anti G appears to bind to D, C, and G
Many others
ALLELIC DELETIONSALLELIC DELETIONS No Cc and/or Ee epitopes
DC-, Dc-, D-E, D-- Enhanced or exalted D Ag expression
Rhnull (no Rh Ag expression at all) ---/--- (double bar rr) Or, because of independently inherited
suppressor genes If exposed to any Rh Ags, make Abs to
those and to Rh 29 (“pan” or “total” Rh) Causes a mild hemolytic anemia
Rhmod - weakened expression of all Rh Ags
Rh ANTIBODIESRh ANTIBODIES
Immune IgG Abs (IgG1 and IgG3 most important)
React optimally at 37oC or with AHG Order of immunogenicity:
D > c > E > C > e Do not bind complement (RBC destruction by
Rh Abs is extravascular)
Rh Abs: Rh Abs: CLINICAL SIGNIFICANCECLINICAL SIGNIFICANCE
Severe HDN Severe transfusion reactions