C4d deposition in cardiac allografts correlates with alloantibody.
BACKGROUND
The presence of C4d along the peritubular capillaries in kidney allografts correlates with the presence of anti-donor serum alloantibodies. We applied C4d staining to cardiac allograft and non-allograft biopsies to determine if C4d staining in heart allografts correlates with anti-donor serum alloantibodies.


METHODS
We stained for C4d all available frozen tissue biopsies from cardiac transplant recipients between 1997 and 2002, including autopsies. Two hundred twenty-one tissue samples from 124 patients were analyzed. Included in both groups were a variety of International Society for Heart and Lung Transplantation (ISHLT) grades of rejection plus post-implant cardiac ischemic injury (PIMI), and biopsies from patients who had received OKT3. Patients were matched by age, gender and interval after transplantation. Forty-four additional controls were included from patients biopsied for non-transplant-related cardiac disease.


RESULTS
C4d staining of the myocardial capillaries correlated well with the presence of anti-donor alloantibodies. Twenty-one of 25 biopsies from patients with anti-donor alloantibodies showed C4d staining (84%), whereas only 7 of 60 without anti-donor alloantibodies stained for C4d. C4d staining did not correlate with ischemia or OKT3 therapy. Only 4 of 44 non-transplant biopsies stained for C4d (9%). An example of the clinical utility of C4d staining in patient care is presented.


CONCLUSIONS
C4d staining of the capillaries in cardiac allografts correlates well with anti-donor serum alloantibodies, is a useful assay to verify alloantibody deposition, and can be used to establish one of the criteria for antibody-mediated cardiac rejections.
Smith
Rex Neal
RN
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA. smith.rex@mgh.harvard.edu
Brousaides
Nicole
N
Grazette
Luanda
L
Saidman
Susan
S
Semigran
Marc
M
Disalvo
Thomas
T
Madsen
Joren
J
Dec
G William
GW
Perez-Atayde
Antonio R
AR
Collins
A Bernard
AB
D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism; D004396:Coloring Agents; D015935:Complement C4b / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000378:metabolism*; D016853:Muromonab-CD3 / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000209:etiology / Q000276:immunology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism*
D015415:Biomarkers; D004396:Coloring Agents; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016853:Muromonab-CD3; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d