Utility of routine immunofluorescence staining for C4d in cardiac transplant recipients.
BACKGROUND
Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care.


METHODS
This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwent > or = 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection.


RESULTS
Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p < 0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p < 0.01 for each).


CONCLUSIONS
Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.
Gupta
Sachin
S
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9047, USA.
Mitchell
Joshua D
JD
Lavingia
Bhavna
B
Ewing
Gene E
GE
Feliciano
M Nicholas
MN
Kaiser
Patricia A
PA
Ring
W Steves
WS
Stastny
Peter
P
Patel
Parag C
PC
Markham
David W
DW
Mammen
Pradeep P A
PP
Dimaio
J Michael
JM
Drazner
Mark H
MH
D000328:Adult; D000368:Aged; D001706:Biopsy; D015935:Complement C4b / Q000276:immunology*; D003955:Diagnostic Tests, Routine; D005260:Female; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D012189:Retrospective Studies
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d