C4d Deposition in Cardiac Allografts Correlates With Alloantibody
Received 26 March 2004; received in revised form 16 June 2004; accepted 4 July 2004. published online 16 May 2005.
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 Transplanatation (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.
aDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
bDepartment of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
cDepartment of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
dChildren’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Reprint requests: Rex Neal Smith, MD, Department of Pathology, Massachusetts General Hospital, 501D Warren Building, Boston, MA 02114-2696. Telephone: 617-726-1835. Fax: 617-726-2365.