This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wehner, J. Articles by Baldwin, W. M. Search for Related Content PubMed PubMed Citation Articles by Wehner, J. Articles by Baldwin, W. M., III Related Collections Animal models of human disease Mechanism of atherosclerosis/growth factors Other Vascular biology

(Circulation Research. 2007;100:191.)
© 2007 American Heart Association, Inc.

Reviews

Antibody and Complement in Transplant Vasculopathy

Jennifer Wehner, Craig N. Morrell, Taylor Reynolds, E. Rene Rodriguez, William M. Baldwin, III

From the Departments of Pathology (J.W., T.R., W.M.B.) and Comparative Medicine (C.N.M.), Johns Hopkins University School of Medicine, Baltimore, Md; and the Department of Pathology (E.R.R.), Cleveland Clinic Foundation, Ohio.

Correspondence to William M. Baldwin III, MD, PhD, Department of Pathology, Ross Research Bldg, Rm 659, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205-2196. E-mail wbaldwin{at}jhmi.edu

This review is part of a thematic series on Transplant Vasculopathy, which includes the following articles:

Allograft Vasculopathy Versus Atherosclerosis
Antibody and Complement in Transplant Vasculopathy
Cytokines, Interferon-, and Transplant Vasculopathy
Chemokines and Transplant Vasculopathy
Stem Cells and Transplant Vasculopathy

William M. Baldwin III and Jordan Pober Guest Editors

Advances in immunosuppression have decreased the incidence of acute rejection, but the development of vasculopathy in the coronary arteries of transplants continues to limit the survival of cardiac allografts. Transplant vasculopathy has also been referred to as accelerated graft arteriosclerosis because it has features of arteriosclerosis, but it is limited to the graft and develops over a period of months to years. Although the pathological features of transplant vasculopathy are well defined, the causative mechanisms are not completely understood. This review focuses on the mechanisms by which antibody and complement can cause or contribute to coronary vasculopathy in cardiac transplants. Antibodies and complement can have independent effects, but the combination of antibodies and complement with inflammatory cells has greater pathogenic potential for the endothelial and smooth muscle cells of the coronary arteries. For example, stimulation through receptors for IgG or complement split products can activate macrophages, but stimulation through combinations of these receptors generates synergistic results. Together, antibodies and complement efficiently integrate the activation of endothelial cells, platelets, and macrophages, which are 3 of the primary components in the pathogenesis of transplant vasculopathy. Recent findings indicate that antibodies and complement produced within the transplant may contribute to vascular pathology in some transplants. Acute rejection caused by antibodies and complement has been treated by combinations of plasmapheresis, intravenous -globulin and monoclonal antibodies to CD20 on B lymphocytes. The effect of these treatment modalities on the development of coronary vasculopathy is unknown.

Key Words: antibodies • complement • platelets • macrophages • coronay arteries

This article has been cited by other articles:

				S. M. Faust, G. Lu, S. C. Wood, and D. K. Bishop TGF{beta} Neutralization within Cardiac Allografts by Decorin Gene Transfer Attenuates Chronic Rejection J. Immunol., December 1, 2009; 183(11): 7307 - 7313. [Abstract] [Full Text] [PDF]

				A. R. Kinderlerer, I. Pombo Gregoire, S. S. Hamdulay, F. Ali, R. Steinberg, G. Silva, N. Ali, B. Wang, D. O. Haskard, M. P. Soares, et al. Heme oxygenase-1 expression enhances vascular endothelial resistance to complement-mediated injury through induction of decay-accelerating factor: a role for increased bilirubin and ferritin Blood, February 12, 2009; 113(7): 1598 - 1607. [Abstract] [Full Text] [PDF]

				D. Schmauss and M. Weis Cardiac Allograft Vasculopathy: Recent Developments Circulation, April 22, 2008; 117(16): 2131 - 2141. [Abstract] [Full Text] [PDF]

				M. L. Rose Interferon-{gamma} and Intimal Hyperplasia Circ. Res., September 14, 2007; 101(6): 542 - 544. [Full Text] [PDF]