C4d Deposition in Cardiac Allografts Correlates With Alloantibody

Smith, Rex Neal; Brousaides, Nicole; Grazette, Luanda; Saidman, Susan; Semigran, Marc; Disalvo, Thomas; Madsen, Joren; Dec, G. William; Perez-Atayde, Antonio R.; Collins, A. Bernard

doi:10.1016/j.healun.2004.07.021

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 24, Issue 9 , Pages 1202-1210, September 2005

C4d Deposition in Cardiac Allografts Correlates With Alloantibody

Rex Neal Smith, MD
- Department of Pathology, Massachusetts General Hospital, 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.
Nicole Brousaides, BS
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
Luanda Grazette, MD
- Department of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
Susan Saidman, PhD
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
Marc Semigran, MD
- Department of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
Thomas Disalvo, MD
- Department of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
Joren Madsen, MD
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
G. William Dec, MD
- Department of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
Antonio R. Perez-Atayde, MD
- Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.
A. Bernard Collins, BS
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA

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.