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 survival of cardiac transplants, and ischemic changes in early posttransplantation endomyocardial biopsies correlate with the later development of chronic rejection. In animal models, tissue ischemia has been shown to activate complement.


METHODS
To determine whether ischemic changes in endomyocardial biopsies were associated with complement deposition, biopsies obtained 1-3 weeks after transplantation from 33 patients were evaluated immunohistologically for C4d and C3d deposition as well as for IgM, IgG, and IgA. The histological changes associated with ischemic injury were scored independently, using previously reported criteria without knowledge of the immunohistochemical results.


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 ischemic 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 IgG 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 of the 18 biopsies without C4d or C3d deposition had moderate acute rejection. However, C4d and C3d deposition did correlate with repeated acute rejection episodes on subsequent biopsies.


CONCLUSIONS
Thus, ischemic changes are associated with the activation of complement. Complement activation may in turn promote tissue injury and provide a potential target for future treatment.
Baldwin
W M
WM
Department of Pathology, The Johns Hopkins University, Baltimore, Maryland 21205-2196, USA. wbaldwin@welch.jhu.edu
Samaniego-Picota
M
M
Kasper
E K
EK
Clark
A M
AM
Czader
M
M
Rohde
C
C
Zachary
A A
AA
Sanfilippo
F
F
Hruban
R H
RH
D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions; D001706:Biopsy; D002315:Cardiopulmonary Bypass; D015933:Complement C3d / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006084:Graft Rejection / Q000378:metabolism; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D016612:Paraffin Embedding; D010446:Peptide Fragments / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors
D003181:Complement C4; D007136:Immunoglobulins; D010446:Peptide Fragments; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d; D003165:Complement System Proteins