Transcript Blood group antigens assigned to systems

Histo-blood group antigens as
allo- and/or autoantigens
Nydegger, U.E. and Flegel, W.A.
University of Bern, Switzerland and University of Ulm, Germany
[email protected] - www.immune-complex.ch
4th International Congress Autoimmunity Budapest 2004
Blood group antigens assigned to systems
60
Intrinsic antigens defined by
red cell membrane proteins
Intrinsic antigens defined by
glycosyltransferase genes
Acquired antigens (not
intrinsic to red cell)
50
40
Slide courtesy of D. Anstee 1997
No of
30
antigens
20
10
0
ABO
P
LU
LE
JK
YT
SC
CO
CH/RG
XK
CR
IN
World Wide Web sites for Blood Group Antigens
• http://www.bioc.aecom.yu.edu/bgmut/index.htm
• http://www.uni-ulm.de/~wflegel/RH/
• http://jove.prohosting.com/~scarfex/blood/groups.html
Nydegger UE, Flegel WA 2004
Blood group antigens as autoantigens
• I/i
• Cold agglutinins
• P
• Cold agglutinins
• Donath-Landsteiner antibodies
• Warm-reactive autoantibodies
• Kell
• Lewis
• Helicobacter pylori
– molecular mimicry
• MN
• Treponema pallidum
– molecular mimicry
Nydegger UE, Flegel WA 2004
Blood groups on the RBC
Lutheran
Knops
ABO
Ii
Gerbich
Diego
Yt
Duffy
MNS
Cromer
Indian
Kell
Rh
LW
Slide courtesy of E. Sjoberg-Wester
Chemical basis
of the ABO and Lewis blood group system
Type 1 Precursur
Substance
ba11
B
A
Htype
type
Le
Le
O
O
O
O
OH
NH
O
O
O
O
O
NH
O
ß(1-3)
Gal
ß
R
-D-GalNAc(1-3)
-L-Fuc(1-2)
-D-Gal(1-3)
ß-D-Gal(1-3)[-L-Fuc(1-4)]ß-D-GlcNAc
ß-D-Gal(1-3)[-L-Fuc(1-4)]ß-D-GlcNAc
[-L-Fuc(1-2)]
[-L-Fuc(1-2)]
ß-D-Gal(1-3)ß-D-GlcNAc
-L-Fuc(1-2)
ß-D-Gal(1-3)ß-D-GlcNAc
ß-D-Gal(1-3)ß-D-GlcNAc
Nydegger UE, Flegel WA 2004
O
O
O
B type
O type
Monoclonal antibodies
O type
Lectin
Koestner et al. Lancet 363(2004)1523
Months post transplant
14 2
Controls 36 30
Disappearance of B and
appearance of H Antigen
ABOI heart allograft: follow up for 44
months post transplant
B Antigen
Post transplant: 12
24
36
44 months
Nydegger UE, Flegel WA 2004
H Antigen
Conclusion
• Numerous blood group system antigens
– occur not only on red blood cells
– but are also expressed on cells of various other tissues
• Hence, autoantibodies
– known to impinge on red cells
– are also reactive for various other tissues
• Blood group antigens
– might be more frequently involved as tissue autoantigens
– and should be more often considered in this context
Nydegger UE, Flegel WA 2004