Week 2: RH Blood Group System

rhesus factor

the Rh antigen

Rh positive

D antigen present

Rh negative

NO D antigen

how many RBC antigens are in the Rh blood group system?

around 50

what conditions can be caused related to the D antigen?

1. severe hemolytic disease of the newborn

2. hemolytic transfusion reactions

most common antigens in Rh system

D, C, E, c, e

immunogenicity order of common antigens in Rh system

D > E > c > C > e

will everyone who comes into contact with foreign RBCs develop antibodies?

no

what is generally the most common Rh antigen type seen across demographics?

e

what is generally the most least Rh antigen type seen across demographics?

E

immune antibodies against Rh antigens are not ____________ occurring

naturally

a person must be __________ to an Rh system antigen on foreign RBCs to develop an antibody to it

exposed

Rh negative people will not automatically have _________

anti-D

what type of Ig are the antibodies of the Rh system?

IgG

what temperature to the antibodies of the Rh system react best at?

37C

antibodies of the Rh system can cross the ___________

placenta

___________ hemolysis can result from hemolytic transfusion reactions

extravascular

dosage

when antibodies react better with homozygous cells than heterozygous cells

may antibodies of the Rh system exhibit dosage?

yes

antibody reactions of the Rh system are enhanced by ____________ treated cells

enzyme

antibodies of the Rh system do not bind _____________

complement

the 2 genes __________ and __________ on chromosome ____ are responsible for Rh antigen production

RHD, RHCE, 1

function of RHAG gene (chromosome 6)

encodes for production of Rh-associated glycoprotein

C and c / E and e are inherited in a ___________ manner

codominant

is the D gene dominant or recessive?

dominant

Fisher-Race nomenclature

1. DCE

2. thought that 3 separate genes are inherited together

Weiner or Rh-Hr nomenclature

one gene at a single locus on each chromosome codes for the production of multiple antigens

Weiner nomenclature: single prime (‘)

C or c

Weiner nomenclature: double prime (‘‘)

E or e

Weiner nomenclature: rh refers to ___________; hr refers to __________

C or E, c or e

Weiner nomenclature: Rh0 refers to what?

D

Rz

DCE

R1

DCe

R2

DcE

Ro

Dce

ry

dCE

r’

dCe

r’’

dcE

r

dce

DCE

Rh0 rh’ rh’’

DCe

Rh0 rh’ hr’’

DcE

Rh0 hr’ rh’’

Dce

Rh0 hr’ hr’’

dCE

rh’ rh’’

dCe

rh’ hr’’

dcE

hr’ rh’’

dce

hr’ hr’’

most common haplotype in whites, native americans, and asians

R1 or DCe

most common haplotype in black people

Ro or Dce

most common Rh negative haplotype

r or dce

ISBT terminology

universal 6 digit number given to blood group antigens

Rh antigen testing is only performed for the non-D antigens once an ___________ develops

antibody

saline reactive anti-D reagent

1. IgM

2. low protein

3. can test IgG antibody-coated RBC

4. costly, unavailable, lengthy incubation, no weak D testing

high-protein based anti-D reagent

1. not used much anymore

2. IgG in high protein medium with potentiators

3. shorter incubation, can test weak D

4. false positives, need to run Rh control

chemically-modified low-protein anti-D reagent manufacturing

1. 1970s

2. IgG with cleaved S-S bonds

3. no Rh control needed if ABO antisera is run at same time

monoclonal/polyclonal anti-D reagent manufacturing

1. single clones of myeloma-hybridized cells → max production

2. might blend IgG and IgM to detect at IS or weak D

Rh discrepancies: what can result from these issues?

• incorrect reagent

• forgot to add anti-D

• over-shaking tubes

• deteriorated reagents

• in vivo coating of immunoglobulin

false negative

Rh discrepancies: what can result from these issues?

• incorrect reagent

• fibrin interference

• rouleaux from high protein

• cold agglutinins

• contamination

false positive

weak D phenotype

when Rh positive cells don’t react or weakly react with anti-D at immediate spin

a weak D phenotype will agglutinate if the test is taken through ___________________ phase

anti-human globulin

causes of weak D phenotype

1. genetics

2. C trans

3. partial or mosaic D

genetic weak D

1. reduced D antigen sites

2. cannot make anti-D

3. rare (black > white)

C trans weak D

1. gene interaction effect

2. ex: Dce/dCe or Dce/dCe

3. cannot make anti-D

partial or mosaic D

1. D antigen has multiple epitopes, or can be missing epitopes

2. tests + or - depending on what’s missing and the antisera reagent

3. CAN make anti-D to missing epitope

with what groups do we do weak D testing?

donors and neonates

we do not want to transfuse an Rh negative patient with a __________ positive RBC

weak D

Rh negative mothers who give birth to _________ positive neonates can develop anti-D

weak D

how does weak D testing work?

1. anti-D reagent added

2. IS is negative

3. incubate at 37 → still negative

4. saline wash

5. AHG added → + or - confirms presence of D antigen

what is the control ran with weak D testing?

Rh control, which should test negative with patient RBCs

Cw antigen

1. low incidence antigen

2. 2% white

G antigen

1. present on most D+ and all C+ RBCs

2. antibody acts like a mix of anti-C and anti-D

3. important testing for women with pregnancy

f antigen

present if c + e on same chromosome

which Weiner Rh blood system groups have the f antigen?

r or Ro

rhi antigen

present if C + e on same chromosome

which Weiner Rh blood system groups have the rhi antigen?

R1 or r’

how do the rhi and f antigens or their antibodies help us determine?

the genotype of the patient

if a patient develops anti-f, they do not have the _____ antigen

f

Rhnull

1. none of the Rh antigens are expressed on RBCs

2. also —-/—-

3. mutation in RHAG gene + normal RHD / RHCE or…

4. deletion of RHD gene + mutations in each RHCE gene

deletion phenotypes with Rh antigens

1. lacks one or more of the Rh antigens

2. written as -DE, -De, CD-, cD-, -D-

what are the possible genotypes for this phenotype in Fisher Race nomenclature?

• anti-D: +

• anti-C: +

• anti-E: 0

• anti-c: +

• anti-e: +

1. either DD or Dd

2. Cc

3. ee

4. result = DCe/Dce, DCe/dce, or Dce/dCe

of DCe/Dce, DCe/dce, or Dce/dCe, what is the most probably genotype in Fisher Race and Weiner nomenclature for white populations?

R1r or DCe/dce

of DCe/Dce, DCe/dce, or Dce/dCe, what is the most probably genotype in Fisher Race and Weiner nomenclature for black populations?

RoR1 or Dce/DCe

what is the probability of a child born from an R1R2 Father and R1r Mother will be Rh +?

100%