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Complement in acute liver allograft rejection Eighth Banff Conference on Allograft Pathology Edmonton 2005 A. Dankof Institute of Pathology

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Complement in acute liver allograft rejection Eighth Banff Conference on Allograft Pathology Edmonton 2005 A. Dankof Institute of Pathology Universitätsmedizin Berlin, Charité. Introduction.

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slide1

Complement in acute liver

allograft rejection

Eighth Banff Conference on Allograft Pathology

Edmonton 2005

A. Dankof

Institute of Pathology

Universitätsmedizin Berlin, Charité

slide2

Introduction

In the past the liver has been regarded to be resistant to antibody-associated rejection. Rejection mechanisms were accepted to be almost always based on T-cell mediated immunoresponse.

(Michaelis et al., Springer Semin Immunopathol 2003)

Several studies demonstrated an association of circulating anti-donor antibodies with rejection and graft loss.

(Bishara et al., Hum Immunol 2002; Scornik et al., Am J Transplant 2001; Takakura et al., Clin Transplant 2001)

B-lymphocytes in liver tissue obtained from one patient with ACR expressed a restricted Vh-gene repertoire with a selected pattern of somatic mutations.

(Moeller et al., Virchows Arch 2005)

slide3

MAC and CD59

Conti F, Grude P, Calmus Y, Scoazec JY, Journal of Hepatology 1997

slide4

MAC and CD59

Lautenschlager I, Höckerstedt K, Meri S, Journal of Hepatology 1999

slide5

MAC and CD59

Lautenschlager I, Höckerstedt K, Meri S, Journal of Hepatology 1999

slide6

C4d

N = 15

Pre LTX

Immunohistochemical single staining

C4d, CD20, CD138

LTX

ACR

N = 15

Krukemeyer M, Moeller J, Morawietz L, Rudolph B, Neumann U, Theruvath T, Neuhaus P, Krenn V, Transplantation 2004

slide7

C4d

C4d

C4d deposits were detected in severely inflamed portal tracts of 5 biopsies from patients with ACR (n=5).

slide8

CD20

CD20

CD138

CD138

B-lymphocytes and plasma cells

Pre LTX

ACR

Pre LTX

ACR

slide9

B-lymphocytes and plasma cells

p(CD20) = 0.002

p(CD138) = 0.02

slide10

Immunohistochemical single staining

C4d, CD68, CD20, CD38

Immunohistochemical/immunofluorescence double staining

C4d/CD68

N = 13

Control

N = 22

N = 22

ACR

C4d

Dankof A, Schmeding M, Morawietz L, Günther R, Krukemeyer M, Rudolph B, Koch M, Krenn V, Neumann U, Virchows Archiv 2005

slide11

C4d

C4d

p= 0.013

C4d

slide12

CD68/Macrophages

*

**

ACR/C4d+ CD68

*p = 0.007

**p = 0.007

slide13

C4d and CD68

CD68/C4d

CD68/C4d

slide14

B-lymphocytes and plasma cells

CD20

CD38

p(CD20) = 0.029

p(CD38) = 0.014

slide15

Control

ACR

HCV

N = 29

N = 34

N = 34

Immunohistochemical single staining

C4d

C4d

slide16

C4d

p<0,001

slide17

C4d

mild

moderate

severe

ACR

ACR

ACR

N = 16

N = 14

N = 5

Immunofluorescence

C4d

Sawada T, Shimizu A, Kubota K, Fuchinoue S, Teraoka S, Clin Transplant 2005

slide18

C4d

  • Mild rejection detection of C4d in the portal areas in some cases
  • Moderate rejection detection of C4d in sinusoids, portal veins and portal arteries
  • Severe rejection  detection of C4d in lobules and portal areas
summary
Summary
  • C4d deposits are detectable in a great portion of patients with acute liver allograft rejection.
  • Detection of C4d is associated with an increased number of macrophages in the portal tracts.
  • The distribution pattern of C4d deposits and its association with rejection severity grade remain controversial.
slide20

Conclusion

Immunologically there is more to acute liver allograft rejection than pure T-cell mediated immunoresponse.

The detection of C4d supports the existence of humorally mediated mechanisms in acute liver allograft rejection.

acknowledgements
Acknowledgements

Department of Surgery, Charité Universitätsmedizin Berlin

Ulf Neumann Maximilian Schmeding Peter Neuhaus

Institute of Pathology, Charité Universitätsmedizin Berlin

Gabriele Fernahl Raphaela Günther Janine Karle Martin Koch Manfred Krukemeyer Lars Morawietz Birgit Rudolph Veit Krenn

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