Rh Blood Group System 2r 4g3w6d

Rh blood group system 2 • Describe the causes and effects of: Weak D; partial D; Rh null. • Predict the reactions of antibodies to compound antigens with the common Rh genotypes. • Discuss the usefulness of compound antibodies in determining genotypes.

Overview Weak D Partial D Rhnull Compound antigens Separating a mixture of antibodies LW

Weak D Antigen. • Single amino acid switch in transmembrane region of the RHD protein. • Reduced expression of all epitopes. • Do not produce allo-anti-D. • Can immunise RhD neg recipients.

RHD positive as recipients or donors.

RBC

Weak D Inheritance of C in trans to D, weakens expression of D antigen. antigen

position “Ceppellini” effect R2r’

R1R0

RHD

R0r’

R2Ro

R1r’

R1R2

Partial D phenotype. • Missense mutation in RHD leads to partial expression or absence of some epitopes. • Can form anti-D.

RBC

• Can immunise RHD neg individuals. RHD neg as recipients RhD positive as donors.

RBC

Rhnull phenotype • RBCs lack all Rh antigens. • Have defective RBC membrane:

• altered RBC shape, ↑osmotic fragility, ↓lifespan.

• Can produce anti-RH29 if immunised by transfusion. • S, s, U, and LW antigens are also affected.

1961, Vos et al

Amorphic Rhnull

Homozygous inheritance of inactivating mutation on CE locus in an RHD neg individual. R1-

DCeDcE DCcEe

R1R2

R2-

DCe DCed--

DcE DcEd--

DCed-DCe

d--DcE DcE

R1-

-R2

d-- d----/-----/---

Rhnull Regulator type Mutations in RHAG Reduced amounts of RHAG

Total absence of RHAG

Reduced Rh antigen expression

Rh antigens not expressed

Rhmod

Rhnull

Compound (cis) antigens Additional antigen present when genes are inherited in cis. Cis antigen ce (RH6) Ce (RH7) cE (RH27) CE (RH22)

Antibodies

• • • •

Haplotype R0 : r R1 : r’ R2 : r’’ RZ : ry

Rare. Anti-f (ce) is more common. Marked dosage effects. Inseparable.

Compound (cis) antibodies Used to determine inherited genotypes or haplotypes. Cells tested with antiD C E c e +

+

+

+

+

Phenotype DCcEe

Possible Genotypes DCe/DcE Dce/dCE DCE/dce R1R2 R0ry Rzr

Compound (cis) antibodies Anti-Ce

Anti-cE

Anti-CE

Anti-ce

R 1R 2

3

3

0

0

R0RZ

0

0

3

3

R0ry

0

0

3

3

R2r”

0

4

0

0

R 1R 1

4

0

0

0

r”r” rr’

0

4

0

0

3

0

0

3

rr

0

0

0

4

G antigen

(RH12)

• Mostly found on RBCs with D or C antigen. – rare D-C-G+ and D+C+G• Common amino acid on both D Haplotype and C antigens. R0 : r • Patients who form anti-C often form anti-G as well. R1 : r ’ • Inseparable anti-CD. R2 : r’’ RZ : r y

Anti-G R 1R 2

4

R 2R 2

4

R 1R 1

4

R 0r

3

rr’ r”r’

3

rr rr

0

rr rr’

0

rr

0

3 0 3

(-RH12)

rr patients transfused with rr’ donor blood often form anti-C + anti-G rr patients transfused with R0r donor blood often form anti-D + anti-G

Mimicks anti-C + anti-D Inseparable

Adsorption

C positive D negative RBCs incubated with Patient’s serum.

Y

Y Y Y Y Y Y Y Y Anti-D Y C+ D-

C+ D-

Anti-G

Y Y

C+ D-

C+ D-

Y Y

Y Y

Anti-G adsorbs onto C positive cells leaving anti-D in the serum

C+ D-

Y

Anti-D + anti-G mixture can be separated by adsorption.

C+ D-

C+ D-

Y C+ D-

Y Y

Adsorption

D positive C negative RBCs incubated with Patient’s serum.

Y

Y Y Y Y Y Y Y Y Anti-C Y CD+

CD+

Anti-G

CD+

Y Y

Y

CD+

Y

Y

Y

Anti-G adsorbs onto D positive cells leaving anti-C in the serum

CD+

Y

Anti-C + anti-G mixture can be separated by adsorption.

CD+

CD+

CD+

Y

Y Y

LW • 1963 - RH and LW different Blood Groups (Levine, Cellano et.al) • Chromosome 19p13.3 • Similar serologic properties but not genetically related. • Alleles are LWa, LWb, and LW (amorph).

LW • D positive RBCs from adults express LW more strongly than D negative red cells. • anti-LW made by LW(a-b-) people can mimic anti-D. • All RHnull individuals are LW(a-b-), but not all LW(a-b-) are RHnull

Further reading Daniels G, Bromilow I, Essential guide to Blood Groups, Wiley-Blackwell, Oxford. Overfield J, Dawson D, Hamer D. Transfusion Science 2nd Ed 2008, Scion Blainey and Howard, Basic and Applied Concepts of Immunohematology Ch 5.2nd Ed.MOSBY Elsevier. Missouri Reid ME and Lomas-Francis C, “The Blood Group Antigens FactsBook”, Academic Press Limited, London, 1st Edition, 1997 bbguy.com