Complement deposition in early cardiac transplant biopsies is associated with ischemic injury and subsequent rejection episodes

Background, Prolonged warm or cold ischemia is associated with poor surviva l of cardiac transplants, and ischemic changes in early posttransplantation endomyocardial biopsies correlate with the later development of chronic re jection. In animal models, tissue ischemia has been shown to activate compl ement, Methods. To determine whether ischemic changes in endomyocardial biopsies w ere associated with complement deposition, biopsies obtained 1-3 weeks afte r transplantation from 33 patients were evaluated immunohistologically for C4d and C3d deposition as web as for IgM, IgG, and IgA. The histological ch anges associated with ischemic injury were scored independently, using prev iously reported criteria without knowledge of the immunohistochemical resul ts. Results, Diffuse capillary and pericapillary deposition of C4d or C3d were detected in endomyocardial biopsies of 14 of the 33 patients. The majority of biopsies (79%) with C4d or C3d deposits had histological evidence of isc hemic injury, including eight of the nine biopsies containing both C4d and C3d deposition. In contrast, only 8 of 18 (45%) of the biopsies without C4d or C3d deposition had ischemic injury. Only trace amounts of IgM and no Ig G or IgA were demonstrable in the biopsies. Only 2 of the 14 biopsies with C4d or C3d deposition had evidence of moderate acute rejection, whereas 5 o f the 18 biopsies without C4d or C3d deposition had moderate acute rejectio n, However, C4d and C3d deposition did correlate with repeated acute reject ion episodes on subsequent biopsies, Conclusions. Thus, ischemic changes are associated with the activation of c omplement, Complement activation may in turn promote tissue injury and prov ide a potential target for future treatment.