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good or bad

VIEWS: 6 PAGES: 33

									C4d: Good or Bad?
C4             C4b         C4b              C4d

     C1qrs

                                Factor I
         C4b              C4b
                     C2                    C4d
Saadi et al. J Exp Med 182: 1807, 1995
How to Detect Humoral Rejection
   Dysfunction of graft
   Anti-donor antibodies in the blood
   Ig deposits
   Complement deposits
   Platelet count
   Fibrin
   RBC morphology
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
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
Complement Removes Immune Complexes




Healthy EC              Sick EC
Normal Lung   Transplanted Lung
Spleen   Liver   vWF
                 C3
Complement Repairs Endothelium




        Saadi and Platt J Exp Med 181: 21, 1995
Complement Bocks Reactive Sites

 C4          C4b       C4d




               C4d   C4d   C4d
 C4d   C4d                       C4d
      Accommodation




Anti-A titer 1:64
C4d in Accommodation
        No
        Complement


Complement
Pre-treated
                                       Ca2+             Ca2+

         Ca2+
                   C5a

             ?                         MAC               MAC
         Ca2                                   Raf Ras Gi      STAT Raf
                    Gi                                                 STAT
         +                                                          JAK
                    G      ADENYL                            PLCb2
                    q      CYCLASE
                                                                        STAT
                                                     PI-3K             STAT
 PLCb2
                                                               Atk
                   PI-                        MEK-1
                                cAMP                   DAG
IP                 3K
3            DAG
                                                      ERK-1
                         ERK-                  PKC               S6k
                          1
     Ca2
     +             PKC




                                                 Nucleus
    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
  C1rs         MASP

         MBP
C1q
                            H
                      C3b       Bb
    Organ         Acute Vascular
Transplantation     Rejection


                                   Cellular    Chronic
                                   Rejection   Rejection
  Hyperacute
   Rejection      Accommodation
C4d deposition in peritubular capillaries




        Collins BA, et. al. JASN 10:2208, 2000
 C4d: Good or Bad?
How C4d helps
How complement harms
How complement benefits
Cardiac Xenograft After Kidney Perfusion
    The Need for C4d
Kidneys absorb Ig very well
Bound Ig disappears by endocytosis
    and shedding
Some Ig binds “non-specifically”
       IgM Binding




Lung                 Heart

								
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