Abstract

The development of graft atherosclerosis in heart transplant recipients has been associated with the development of post-transplant cytomegalovirus infection. The mechanism of this involvement, however, remains unclear. I undertook a study to determine the role of cytomegalovirus in the development of graft atherosclerosis. First, a rapid method of detecting cytomegalovirus based on capillary polymerase chain reaction and gel electrophoresis was employed to determine the presence of cytomegalovirus in a wide variety of clinical samples. Detection of cytomegalovirus is a lengthy procedure under normal conditions, and timely detection of cytomegalovirus in transplant recipients may allow intervention early enough to block the development of graft atherosclerosis. Second, post mortem paraffin embedded coronary artery samples of fifteen heart transplant patients were analyzed by the polymerase chain reaction to determine if chronic latent cytomegalovirus infection of the graft vasculature was responsible for the development of graft atherosclerosis.

No patient with graft atherosclerosis had cytomegalovirus positive coronary artery specimens at the time of autopsy. Moreover, one patient who did have cytomegalovirus positive coronary artery specimens had no evidence of graft atherosclerosis at autopsy. Finally, a study was undertaken to determine if cytomegalovirus molecular mimicry of the human leukocyte antigen DR (HLA-DR) beta chain could provide the basis of enhanced immune response against the graft. Complement lysis assays of HLA-DR positive cell lines were performed with a polyclonal serum to the cytomegalovirus antigen (immediate-early-2 antigen) with known five amino acid homology with HLA-DR. Peripheral B cells and a HLA-DR positive cell line were lysed by the serum and complement, while peripheral T cells and a HLA-DR negative cell line were not lysed. Based on these data, a model of cytomegalovirus involvement in the development of graft atherosclerosis is proposed. Cytomegalovirus infection leads to enhanced humoral immunity against graft endothelial cells expressing HLA-DR. Vascular damage to the graft leads to a progressive, proliferative healing response that results in graft atherosclerosis and eventual graft failure.

LLU Discipline

Microbiology

Department

Microbiology

School

Graduate School

First Advisor

John F. Sands

Second Advisor

James D. Kettering

Third Advisor

Sandra Nehlsen-Cannarella

Fourth Advisor

Giuseppe Molinaro

Fifth Advisor

Anthony Zuccarelli

Sixth Advisor

Arthur Hauck

Seventh Advisor

Brian E. Jaski

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1995

Date (Title Page)

6-1995

Language

English

Library of Congress/MESH Subject Headings

Cytomegalovirus Infections; Coronary Arteriosclerosis; Herpesviridae; Graft vs Host Disease; Graft Rejection

Type

Dissertation

Page Count

2; x, 131

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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