histo-blood group antigens as allo- and/or autoantigens nydegger, u.e. and flegel, w.a. university...

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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

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Page 1: 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

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

Page 2: 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

Blood group antigens assigned to systems

0

10

20

30

40

50

60

ABO P LU LE JK YT SC CO CH/RG XK CR IN

No of antigens

Intrinsic antigens defined byred cell membrane proteins

Intrinsic antigens defined byglycosyltransferase genes

Acquired antigens (notintrinsic to red cell)

Slide courtesy of D. Anstee 1997

Page 3: 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

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

Page 4: 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

Blood group antigens as autoantigens

• I/i

• P

• Kell

• Lewis

• MN

• Cold agglutinins

• Cold agglutinins

• Donath-Landsteiner antibodies

• Warm-reactive autoantibodies

• Helicobacter pylori– molecular mimicry

• Treponema pallidum– molecular mimicry

Nydegger UE, Flegel WA 2004

Page 5: 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

Blood groups on the RBC

Gerbich

Knops

Kell

Lutheran

LW

Duffy

MNS

ABOIi

RhIndian

Cromer

Yt

Diego

Slide courtesy of E. Sjoberg-Wester

Page 6: 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

Chemical basisof the ABO and Lewis blood group system

ß-D-Gal(1-3)ß-D-GlcNAc

O

O

O

N

H

O

O

R

ß

Gal

ß(1-3)

Type 1 Precursur Substance

-L-Fuc(1-2) ß-D-Gal(1-3)ß-D-GlcNAc

H type 1

O

O

O

N

H

O

O

A type 1

-D-GalNAc(1-3) [-L-Fuc(1-2)] ß-D-Gal(1-3)ß-D-GlcNAc

B type 1

-D-Gal(1-3) [-L-Fuc(1-2)] ß-D-Gal(1-3)ß-D-GlcNAc

O

O

O

H

O

O

Leb

-L-Fuc(1-2) ß-D-Gal(1-3)[-L-Fuc(1-4)]ß-D-GlcNAcß-D-Gal(1-3)[-L-Fuc(1-4)]ß-D-GlcNAc

Lea

Nyd

eg

ger U

E, F

lege

l WA

200

4

Page 7: 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

Disappearance of B and appearance of H Antigen

Ko

estn

er et al. Lan

cet 3

63(2004)1523

B type O type O typeMonoclonal antibodies Lectin

M

on

ths

po

st t

ran

spla

nt

Co

ntr

ols

36

3

0

1

4

2

Page 8: 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

ABOI heart allograft: follow up for 44 months post transplant

B Antigen

H Antigen

Post transplant: 12 24 36 44 months

Nyd

eg

ger U

E, F

lege

l WA

200

4

Page 9: 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

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