BIOLOGYBIOLOGY

ofof

COMPLEMENTCOMPLEMENT

BIOLOGYBIOLOGYDIAGNOSISDIAGNOSIS

COMPLEMENTCOMPLEMENT

= C4d

= C4d C3 injury

= C4d C3 injury

MBL

ApoptoticCMV cells

CRP

= C4d C3 injury

MBL

ApoptoticCMV cells

CRPRegulators

= C4d C3 injury

MBL

ApoptoticCMV cells

CRPRegulators

protection

C1

C4

C2

C3MBL

B

C5

Classical

Lectin

Alternative

Three Pathways of Complement ActivationThree Pathways of Complement Activation

C1

C4

C2

C3MBL

B

C5

Classical

Lectin

Alternative

Three Pathways of Complement ActivationThree Pathways of Complement Activation

a

a

a

b

b

b

b

a

C1 C2 C5 C6 C7 C8 C9C4 C30.6 mg/ml1.3 mg/ml

C4b

C2a

C3b

Bb

C1 C2 C5 C6 C7 C8 C9C4 C30.6 mg/ml1.3 mg/ml

C1inh

Factor IC4bp CR1

MCP

Factor IDAF CR1

MCP

C4bp

Factor IDAF CR1Factor H

CD59Clusterin

VitronectinC

4bC

2a

C3b

Bb

C3b > C4b CR1iC3b > iC4b CR3

C3d > C4d CR2

FUNCTIONFUNCTION

C4d vs C3d STAININGC4d vs C3d STAINING

0

1

2

3

4

0 1 2 3 4

C3d

C4d

FemaleMaleATGAM

ATGAM

Thymoglobulin

(Horse polyclonal)

(Rabbit polyclonal)

C4d+ / Total

C4d DepositionC4d DepositionATGAM vs ThymoglobulinATGAM vs Thymoglobulin

9 / 9

0 / 8

C Reactive Protein Activation of Complement

CRP- Complement Complexes in Renal TransplantRecipients

ÑÑ

ÑÑ

J J J JH

H

H

H

F F F

F

B B B BÉÉ

É

É

ÇÇ

Ç

Ç

ÅÅ Å

Å3

33

3

â

before day3 before day3 0

50

100

150

200

250

Time Relative to Transplantation

Ñ

Ñ

Ñ

ÑJ

J

J JH

H

H

H

F

F

F

F

B B B B

É

É

É

É

Ç

Ç

Ç

Ç

Å

Å

Å

Å

3

3

3

3â

0

50

100

150

200

250

C4b C3b C4d C3d

J Immunol 157: 473 '96

ANTIBODY ASSOCIATED REJECTION

7 years after transplantation anti-DR7 and DRw53

ANTIBODY ASSOCIATED REJECTION

after plasmapheresis plus IVIg anti-DR7 and DRw53 undetectable

C4d C3d

B

B

Ñ

Ñ

H

H

Ç

Ç

J J

ÉÉ

4 hr 8 hr0

10

20

30

40

50

60

70B iC3b

Ñ (+IL-1)

H C3d

Ç (+IL-1)

J ICAM

É (+IL-1)

Clearance of iC3b and C3dClearance of iC3b and C3dfrom Human Endothelial Cells in vitro

“SUBLYTIC” MACLEUKOCYTE ACTIVATION BY

MAC

Endothelial

ACTIVATION OF ENDOTHELIAL CELL BY MAC

W-P

MAC

Endothelial

ACTIVATION OF ENDOTHELIAL CELL BY MAC

P-selectinvWfCD63

TissueFactor

MAC

Endothelial

ACTIVATION OF ENDOTHELIAL CELL BY MAC

P-selectinvWfCD63

TissueFactor

Synthesis

PAFMCP-1

bFGF

P-selectin

TissueFactor

PDGF

IL-8

MAC

Endothelial

P-selectinvWfCD63

TissueFactor

Synthesis

PAFMCP-1

bFGF

P-selectin

TissueFactor

PDGF

IL-8

Monocyte/Macrophage

Patelet

P-selectinbFGFPDGF

vWfTissueFactor

TNF

B. Wasowska et al 2001 Transplantation 71, 727.

vWf

Ig Knock Out Recipients

0

10

20

30

40

50

60

70

80

90

100

SLENormal

Tan et al. Arth & Rheum 40: 1601-1611, 1997

1:3201:1601:801:40

Operating Characteristics of Operating Characteristics of ANA Immunofluorescence AssaysANA Immunofluorescence Assays

HUMORAL IMMUNITY IN HUMORAL IMMUNITY IN CARDIAC TRANSPLANTSCARDIAC TRANSPLANTS

Cardiac Surgery:J. Conte Cardiology:D Carter, EK Kasper, D Judge Immunogenetics:D Lucas, MS Leffell, AA Zachary Bioengineering:J Haun, R AlevriadouPathology:RH Hruban, ER Rodriguez, WM Baldwin III