C4d: Good or Bad

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C4d Good or Bad?
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C1qrs
Factor I
C2
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Saadi et al. J Exp Med 182 1807, 1995
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How to Detect Humoral Rejection
Dysfunction of graft Anti-donor antibodies in the
blood Ig deposits Complement deposits Platelet
count Fibrin RBC morphology
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What Could Be Good About C4d?
Complement, particularly C4, inhibits humoral
immunity Complement removes immune complexes C4d
blocks reactive sites Complement repairs
endothelium Complement and/or Ab induces
Accommodation
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Regulation of Humoral Immunity by C4 and its
Receptors
CR2 (C4b receptor) suppresses auto-immunity C4
Facilitates clearance of immune complexes SLE
associated with C4 deficiency C4 deficiency
Impairs clearance of apoptotic cells
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Complement Removes Immune Complexes
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Normal Lung
Transplanted Lung
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vWF
C3
Liver
Spleen
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Complement Repairs Endothelium
Saadi and Platt J Exp Med 181 21, 1995
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Complement Bocks Reactive Sites
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Accommodation
Anti-A titer 164
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C4d in Accommodation
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No Complement
Complement Pre-treated
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Caveats of Accommodation
May allow organ to survive long enough to acquire
chronic rejection May fail to avert whatever
causes chronic rejection May cause chronic
rejection
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MASP
C1rs
MBP
C1q
H
C3b
Bb
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C4d deposition in peritubular capillaries
Collins BA, et. al. JASN 102208, 2000
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C4d Good or Bad?
How C4d helps How complement harms How
complement benefits
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Cardiac Xenograft After Kidney Perfusion
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The Need for C4d
Kidneys absorb Ig very well Bound Ig disappears
by endocytosis and shedding Some Ig binds
non-specifically
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IgM Binding
Lung
Heart