:

RHESUS (Rh)
5

. .
-

2012

1939 Levine & Stetson ( / )
1940 Wiener & Peters ( )
1940 Wiener & Landsteiner ( Rh

Macacus Rhesus)
1941 Wiener & Landsteiner {85% Rh (+)}
1961 anti-Rh Abs # anti-Rh Abs M. Rhesus
Wiener & Landsteiner Rh
LW
 o Rhesus

50 Rh
5 ( )
D
Rh (+) Rh(-) ???
C
c
E
e
o Rhesus

()
 o Rhesus
Source: Transfusion and Apheresis Science 2011; 44:81-91 (DOI:10.1016/j.transci.2010.12.013 )

Rh30 are erythrocyte integral membrane nonglycosylated, palmitoylated proteins, with an apparent molecular
weights, 32 and 35 kDa. Rh30 polypeptides are components of a membrane complex of erythrocyte
membrane proteins including Rh50 glycoprotein and LW, Fy, CD47 and GPB proteins. Interaction with
Rh50 is essential for the expression of RhCED antigens
 o Rhesus


&
85% Rh (+)
gs Rh

C, c & E, e :
Cc, CC, cc, Ee, EE, ee


c C C C c c

e E E E e e
 Rh-Ags

D: 85% Caucasians, 92% Blacks, 99% Asians

C: 68% Caucasians, 27% Blacks, 93% Asians

E: 29% Caucasians, 22% Blacks, 39% Asians

c: 80% Caucasians, 96% Blacks, 47% Asians

e: 98% Caucasians, 98% Blacks, 96% Asians

 Fisher
3
Ags C, c, D,
E, e

1
3

D/d, C/c, E/e

D Ag-D
C Ag-C
c Ag-c
E Ag-E
e Ag-e
d Ag
anti-d
 Fisher
The two notations for the Rhesus antigens from Fisher (1947)
 Fisher's 1943 solution to the Rhesus complex

Edwards A W F Genetics 2007;175:471-476

 Fisher
:
D, c, e

Fisher

Rhesus (+) Rhesus (-)

DCe dce
DcE dCe
Dce dcE
DCE dCE
Commemorative window to Fellows in
Caius College, Cambridge, UK. Clockwise
from top left: C. S. Sherrington, John Venn,
George Green, James Chadwick, R. A.
Fisher, and F. H. C. Crick.
 Wiener
Ags Rh 3

(R1, R2,
R0, )
Fisher

Fisher Wiener
DCe R1
DcE R2
Dce R0
DCE Rz
dce R
dCe r
dcE r
dCE ry
 Wiener - Fisher
 Tippett
1986

(RhD, RhCE)

DNA (2001)
Tippett

1 2

RhD: D

RhCE: C c E e
 Tippett
 RHD RHCE

10 RHD
10 RHCE
 D A

RhAG, RhCE RhD

Rh
RBCs

RBC

Rh
 Rh
D(-)
85% RhD(+) Ag-D

Rh(-) d/d ( Ag-D)

RhD [D(-)]

O RhD [D(-)] ,

 Rh
Dw (D-weak)
RhD(+) Ag-D

Ag-D 10.000-30.000/RBC

D-weak Ag-D 500-1.000 /RBCs

O Dw
( )

 Rh
D-partial D-variant

RhD

Ag-D


D weak

Avent N D , Reid M E Blood 2000;95:375-387

 Rh
Du
O Statton Du Ags-D
anti-D

1. Ags-D <1000/RBC
( ) D-weak

2. Ags-D

( ) D-partial
 Rh
Rhnull
Rh
H Ag-Rh
RBCs ( )

RBCs



(.. Duffy)
 Rhesus
 Rhesus
 Rhesus
 Rhnull
 Rhnull

1. . (r)

r/r RhD, RhCE

2. (Regulator type) Rhmod.

RhD, RhCE
Xor/Xor
Ags
 Southern blot and SSCP
analysis of RH and RHAG loci
in the Rhmod family

Rhmod Syndrome: A Family Study of the Translation-Initiator Mutation

in the Rh50 Glycoprotein Gene
 Rh
Rh-deficiency syndrome
Ags- C, c, E, e

RhCE
RhD
RhCE
 Rh
Rh-deficiency syndrome
 Rh - DEL

RhD RhDel
Ag-D (DEL)
ACGT ACGT
500 < AD-D/RBC
(Asian type DEL)
D

Human RhDel Is Caused by a Deletion of 1,013 bp

Between Introns 8 and 9 Including Exon 9 of RHD Gene
 H Rh (Rh Protein)
RHD RHCE
(>400 )
12
RhD RhCE 35
RhD D (30 )
RhCE
C/c (2 )
E/e (4 )

RhCE
RhCE
2 :
_S103P ( C c Ag),
_P226A ( E e Ag)
 H Rh (Rh Protein)

he Rh genes, showing the 10 exons of RHD and RHCE in opposite orientation on the
chromosome, SMP1 between them, and the Rh boxes flanking RHD. Below that is the D-
negative haplotype, in which RHD is deleted, giving rise to a hybrid Rh box. Bottom.
Diagrammatic representation of the D and CcEe polypeptides, which span the
membrane 12 times and have internal N- and C-termini and six extracellular loops. The
amino acid substitutions that define the C/c and E/e polymorphisms reside in the
second and fourth loops of the CcEe polypeptide, respectively.
 Rh

,
, (
),
Rh(null) ( RhAG)
Rh(null) Abs Rh-Ag (
)
Rh

(aquaporins)
H
(Colton Kidd)
 RhAG RhD

RhD RhAG
 RhAG RhD

RhD RhAG
RhAG RhD
 T ()
Abs Rh :

IgGs

Rh. ;
 Rhesus (anti-Rh)

, IgGs ( IgM), ,

In vitro

1. Ag
1-2
2. Ag-D Ag-E/e Ag-C/c 35

3.

 Abs-Rh (1).
Rh(-) Rh(+)

Abs
6-8

Abs RBCs
( )



Anti-D, anti-C, anti-E, anti-e
()

Rh (D, E, e, C, c)
/

( 45
Ags)

( )

Rh
 Abs-Rh (2).

Hemolytic Disease of the Newborn (DN)

T Anti-D HDN

anti-D

HDN
D C Ag
A HDN anti-C, anti-E
anti-e
 Hemolytic Disease of the Newborn

HDN


IgG

Where does the baby get an antigen that is foreign to
the Mom?
Its the Dads fault!
 HDN

1. Rh System
Antibodies

2. Other Blood
Group Antibodies

3. ABO Antibodies
 HDN

1. RBCs
() RBCs

2. HDN :

3.

4. / /
 Pathogenesis Of Rh Iso-immunisation
Rh Negative Women Man Rh positive (Homo/Hetero)

Rh Neg Fetus
Fetus Rh positive Fetus
No problem

Mother previously sensitized Rh+ve R.B.C.s enter

Secondary immune response Maternal circulation


Non sensitized Mother
? Iso-antibody (IgG) ? Primary immune response


Fetus
Fetus unaffected, 1st
Baby usually escapes.
Haemolysis Mother gets sensitised?

 Pathology Of Iso-immunisation
AFTER BIRTH HAEMOLYSIS IN UTERO

Jaundice ANAEMIA BILLIRUBIN
Kernicterus
Hepatic Failure
HEPATIC MAT. LIV NO
ERYTHROPOESIS EFFECT
DEATH IUD & DYSFUNCTION

ERYTHROBLASTOSIS PORTAL & UMBILICAL VEIN
HYPERTNSION, HEART FAILURE
FETALIS

BIRTH OF AN AFFECTED INFANT - Wide spectrum of presentations. Rapid
deterioration of the infant after birth. May contiune for few days to few months.
Chance of delayed anaemia at 6-8 weeks probably due to persistance of anti Rh
antibodies.


:
;

Rh(-);

RhIg;

Test Mom for ABO, Rh (Weak D), and Antibody

Screen
Group O Mom :

Rh Negative Mom:
Rh Immune Globulin

What is it?

How does it work?

 RhIg

 Rosette Test

:
 Rosette Test -

anti-D (EDTA)
37oC. Anti-D
Rh(+)
R2R2
. R2R2
rosette anti-D
Rh(+)

.
Rosettes
Rosettes;
Rosette
Rosette
 Exchange Transfusion


HDN

IgGs





(;)


RhIg?

Rh positive with anti-K

Baby Rh positive with negative DAT (Direct Antiglobulin
Test)
Mother O negative with anti-C
Baby A negative with positive DAT
Mother A negative with negative IAT (Indirect)
Baby O positive with negative DAT

RhIg?

Mother: A negative with anti-D, C, K

Baby: B positive, +DAT eluate showed D, C

Mother: A negative with negative IAT

Baby: O positive with positive DAT, eluate neg

Mother: AB negative with anti-D

Baby: A negative with negative DAT


Dweak Dpartial;

Dweak

D
Dpartial
D

Fatal hemolytic disease of a newborn due to anti-D in an Rh-positive Du variant mother

 Dweak Dpartial

Rh(+) D

Rh(-) d Rh(-)
d

Rh(-) Abs
( Ag-D
)

Rh(+) Abs
Ag-D

Rh

; D, C, c, E, e

()

-D, -C, -c,

-E, -e
 ;

Abs
Anti-E
Anti-Cweak

Rh


D C c E D C c E

e e

D C c E D C c E

e e
 ABO, Rhesus

1.
2. Rhesus ( D)
3. Kell

:
CcDee (-)
A ccdee (+)
O CCDEe K(-)

d D

c C e e

A B
C C E E
D
A B
c c e e
C c E E
D


1 1

D C c E e D C c E e

1 1

D C c E e D C c E e

:

2 CCDee 1 CCDEE O CCDEE

ccdEe 2 CcDeE 2 CcDeE

CcDeE 1 CcDEe 2 CcDEe 3

1 CCDee 2 CCDEE O CCDEE

ccdEe B CcDeE 1 CcDeE

CcDeE 4 CcDEe 5 CcDEe 6

 A Du

D = Du

Du

D
 Du

Du
anti-D d

Du ;

d
 Du

d Du ;

:
Rh(+) Rh(-)
 Du

; D

-D, NaCl 0.9%,

( IgG).
IgG .
?
O D
D

Du (+)

Du (-)

37 oC
1.
2. 2-5% NaCl 0.9%
3. 2 -D
4. 2
5. 37 oC (15-30 min)
6. 3 NaCl 0.9%
7. (2 )/
8. 1000/ 15-30
9.
10.
11. . 40

 Controls

Rh(+)

D

1. :
ccdee

2.
,
Rh(-)

.
D.
 Gel Test

; A, B, D, C, c
E, e



A, B, D, C, c, E, e, K

?

.




: 1

1.
2. /
Diluent 1 (25 500 /)
3. 10
4. 10
5. 10
6.
7.