(Circulation. 1995;92:205-211.)
© 1995 American Heart Association, Inc.
Articles |
Cardiac Allograft Vasculopathy
Association With Cell-Mediated but Not Humoral Alloimmunity to Donor-Specific Vascular Endothelium
From the Immunobiology Research Laboratory of the Oregon Cardiac Transplant Program; Departments of Medicine and Cell Biology and Anatomy, Oregon Health Sciences University; and Immunology Research, Portland Veterans Affairs Medical Center, Portland, Ore.
Correspondence to Jeffrey D. Hosenpud, MD, Division of Cardiology, Medical College of Wisconsin, 8700 West Wisconsin Ave, Milwaukee, WI 53226.
Background Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease responsible for the majority of late deaths after cardiac transplantation. Although most consider this complication a manifestation of chronic allograft rejection, it has not been established whether this disease is a consequence of humoral or cell-mediated alloreactivity.
Methods and Results Human aortic endothelial cells (HAECs) were
isolated from donor aortas obtained at the time of organ acquisition
for 52 cardiac allograft recipients. Serum and peripheral blood
mononuclear cells were obtained from these 52 allograft recipients at
several time points during the first year after transplantation.
Lymphocyte proliferation (LP) in response to donor-specific HAECs and
alloantibody binding to interferon-
–treated donor-specific HAECs
were performed and correlated with clinical parameters, including HLA
matching, acute cellular rejection, and coronary artery disease on
surveillance angiography. Ten of the 52 patients studied had
angiographic or autopsy evidence of coronary artery disease in the
first posttransplantation year (CAV+ group). The CAV+ group had
higher
LP responses to their donor HAECs at 1 week, 3 months, and 6 months
after transplantation compared with the CAV- group (1 week:
1439±222
versus 824±141 counts per minute [cpm],
P=.026; 3 months:
1282±388 versus 884±94 cpm, P=.07; 6 months:
2504±635
versus 1540±209 cpm, P=.036; CAV+ versus
CAV-,
respectively). Only 8 of the 52 patients had donor-specific
alloantibodies, and there was no relation between antibody presence and
CAV. Other clinical parameters that correlated with CAV included the
level of HLA-DR mismatch and the presence of late acute rejection.
Conclusions CAV is associated with donor-specific cell-mediated alloreactivity to vascular endothelium. Humoral immunity does not appear to have a major role in this disease.
Key Words: transplantation • atherosclerosis • immune system • rejection
This article has been cited by other articles:
 |
|
 |
|
  E. S. Yolcu, X. Gu, C. Lacelle, H. Zhao, L. Bandura-Morgan, N. Askenasy, and H. Shirwan Induction of Tolerance to Cardiac Allografts Using Donor Splenocytes Engineered to Display on Their Surface an Exogenous Fas Ligand Protein J. Immunol., July 15, 2008; 181(2): 931 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Furukawa, S. E Cole, R. V Shah, Y. Fukumoto, P. Libby, and R. N Mitchell Wild-type but not interferon-{gamma}-deficient T cells induce graft arterial disease in the absence of B cells Cardiovasc Res, August 1, 2004; 63(2): 347 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Fischbein, J. Yun, H. Laks, Y. Irie, M. C. Fishbein, B. Bonavida, and A. Ardehali Role of CD8+ lymphocytes in chronic rejection of transplanted hearts J. Thorac. Cardiovasc. Surg., April 1, 2002; 123(4): 803 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Cantin, P. Wen, D. Zhu, M. Dai, S. N. Panchal, M. E. Billingham, J. K. Gwathmey, and H. A. Valantine Transplant Coronary Artery Disease: A Novel Model Independent of Cellular Alloimmune Response Circulation, November 20, 2001; 104(21): 2615 - 2619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Giulia Gagliardi, F Crea, B Polletta, C Bassano, G La Vigna, L Ballerini, and P Ragonese Coronary microvascular endothelial dysfunction in transplanted children Eur. Heart J., February 1, 2001; 22(3): 254 - 260. [Abstract] [PDF]
|
|
|
|
|
|
M. P. Fischbein, A. Ardehali, J. Yun, S. Schoenberger, H. Laks, Y. Irie, P. Dempsey, G. Cheng, M. C. Fishbein, and B. Bonavida CD40 Signaling Replaces CD4+ Lymphocytes and Its Blocking Prevents Chronic Rejection of Heart Transplants J. Immunol., December 15, 2000; 165(12): 7316 - 7322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Y. Wang, I. Aronson, S. Takuma, S. Homma, Y. Naka, T. Alshafie, V. Brovkovych, T. Malinski, M. C. Oz, and D. J. Pinsky cAMP Pulse During Preservation Inhibits the Late Development of Cardiac Isograft and Allograft Vasculopathy Circ. Res., May 12, 2000; 86(9): 982 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Hosenpud, P. Hornick, P. Mason, M. Yacoub, M. Rose, R. Batchelor, and R. Lechler Direct Antigen Presentation and Chronic Rejection • Response Circulation, May 25, 1999; 99 (20): 2709 - 2712. [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Boyle Jr, S. T. Lille, E. Allaire, A. W. Clowes, and E. D. Verrier Endothelial Cell Injury in Cardiovascular Surgery: Atherosclerosis Ann. Thorac. Surg., March 1, 1997; 63(3): 885 - 894. [Abstract] [Full Text]
|
|
|
|
|
|
L. H. Chow, S. Huh, J. Jiang, R. Zhong, and J. G. Pickering Intimal Thickening Develops Without Humoral Immunity in a Mouse Aortic Allograft Model of Chronic Vascular Rejection Circulation, December 15, 1996; 94(12): 3079 - 3082. [Abstract] [Full Text]
|
|