C4d deposition in cardiac allografts correlates with alloantibody

J Heart Lung Transplant. 2005 Sep;24(9):1202-10. doi: 10.1016/j.healun.2004.07.021.

Abstract

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.

Publication types

  • Evaluation Study

MeSH terms

  • Biomarkers / metabolism
  • Biopsy
  • Capillaries / metabolism
  • Coloring Agents
  • Complement C4b / metabolism*
  • Coronary Vessels / metabolism*
  • Fluorescent Antibody Technique
  • Graft Rejection / diagnosis*
  • Graft Rejection / immunology
  • Heart Transplantation / immunology*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies / metabolism*
  • Muromonab-CD3 / therapeutic use
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / immunology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Peptide Fragments / metabolism*

Substances

  • Biomarkers
  • Coloring Agents
  • Immunosuppressive Agents
  • Isoantibodies
  • Muromonab-CD3
  • Peptide Fragments
  • Complement C4b
  • complement C4d