C4d deposition in cardiac allografts correlates with alloantibody

Rex Neal Smith, Nicole Brousaides, Luanda Grazette, Susan Saidman, Marc Semigran, Thomas Disalvo, Joren Madsen, G William Dec, Antonio R Perez-Atayde, A Bernard Collins
Journal of Heart and Lung Transplantation 2005, 24 (9): 1202-10

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.

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