[C4d: a pathogenetically relevant marker in kidney transplantation].
Antibody-mediated allograft rejection should be discriminated from cell-mediated rejection processes since these two distinct pathogenic mechanisms are likely to require different therapeutic approaches. The complement split product C4 d (although biologically inactive by itself) turned out to be a reliable diagnostic marker of antibody-induced complement activation in kidney allografts. In contrast to other organs like heart and bowel, there is no indication that ischemia/reperfusion injury might induce the classical pathway of complement activation in the kidney. Endothelial C4 d deposits in peritubular capillaries of transplanted kidneys are therefore robust indicators of antibody-mediated alloreactivity with potentially unfavourable outcome. The high efficiency of therapeutic strategies aimed at removing alloantibodies from the recipient's circulation (i.e. immunoadsorption and plasmapheresis) in cases of C4d positive rejection further underscores the important pathogenic role of antibodies in renal allograft rejection and the diagnostic relevance of endothelial C4 d deposits. C4 d deposits can also occur de novo in late allograft biopsies. Their association with basement membrane injury in peritubular capillaries and glomeruli, which are the hallmarks of chronic rejection, indicates a contribution of humoral immune reactions to chronic rejection. Due to the clinical relevance of humoral rejection and due to the fact that the latest update of the Banff classification introduced the pathogenically based subdivision of acute rejection into a cell-mediated and an antibody-mediated variant every renal allograft biopsy should be stained for C4 d. It is important to be aware that humoral and cellular rejection often occur simultaneously and that C4d deposits alone are not an unequivocal proof of humoral rejection that immediately requires treatment.
Regele
H
H
Klinisches Institut für Pathologie, Medizinische Universität Wien.
D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002196:Capillaries / Q000473:pathology; D015935:Complement C4b / Q000032:analysis*; D006801:Humans; D007518:Isoantibodies / Q000302:isolation & purification; D016030:Kidney Transplantation / Q000473:pathology*; D010446:Peptide Fragments / Q000032:analysis*; D010956:Plasmapheresis; D015427:Reperfusion Injury / Q000473:pathology; D014184:Transplantation, Homologous / Q000473:pathology
D015415:Biomarkers; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d