The discovery by the group of investigators in the epidemiology and pathobiology departments at the University of Washington’s School of Public Health in Seattle that specific antigenic components of Chlamydia pneumoniae are present in atherosclerotic lesions presents intriguing possibilities concerning the multifactorial nature of the pathogenesis of atherosclerosis. Starting in 1986, this group, headed by Professor Grayston, has been studying this relatively recently identified member of the Chlamydia genus. They quite recently found evidence that the specific antibodies to this pathogen can be identified serologically in the blood of many victims of coronary heart disease and/or myocardial infarction. This supports the results of Saikku et al reported in Lancet in 1988, which were confirmed by the University of Washington group led by Professor Grayston in 1991 and extended in a larger group of patients by Saikku and coworkers in 1992. Now they report very strong evidence that the organism is lurking in the lesions of atherosclerosis and not elsewhere in the artery wall.
The implications of their results published in this issue of Circulation are challenging. The question is, does evidence of the specific antigen and DNA of the organism in the lesion implicate C pneumoniae as either an etiologic agent or a pathogenetic factor in atherogenesis? The finding certainly raises the possibility that C pneumoniae may contribute to the progression of the atherosclerotic lesion. The investigation gains further strength from the use of two monoclonal antibodies, one against a genus antigen and one that is a species-specific reagent, and the finding that when one of these produces a positive result, then the other is also positive. It is also important to note that this immunochemical presence was demonstrated earlier by Kuo et al, long-time associates of Dr Grayston (S Afr Med J. 1992;82:158).
Of interest is the association of these specific antigens with macrophages and smooth muscle cells, the most numerous cells in the developing plaques. It is also important to note that these antigens have not yet been found in normal-appearing arteries or in arteries that usually do not develop atherosclerosis, such as the internal mammary artery.
This group recently extended its study to arteries from young people who died suddenly and unexpectedly, usually from trauma (Proc Natl Acad Sci U S A. 1995;92:6911). No evidence of Chlamydia was noted in the normal-appearing arteries from 31 individuals in that study, which is limited to young people 15 to 34 years of age. In that study, the investigators also used antibody to C trachomatis as a second Chlamydia-derived control antigen and found no evidence of positive species-specific antibody localizing in atherosclerotic lesions. Results from the use of the polymerase chain reaction technique for demonstrating the presence of specific DNA of C pneumoniae were also positive, but in fewer cases than those which gave positive immunocytochemical results.
The results so far raise questions very similar to those commonly asked when reports are published about the presence of viral antigens in atherosclerotic lesions. The biomedical scientific community then frequently asks, are these merely passengers that lodge in diseased tissue (locus minoris resistentia), or do they really have something to do with the cause or progression of the disease? The authors of this present report are well aware of this problem, and they will probably take the important step of seeing what they can do in influencing the development of atherosclerosis with or without hyperlipidemia in a suitable animal model. It is very difficult to rule out the “passenger” role in the human lesion even if one finds negative results in other vulnerable organs or tissues—liver, spleen, lung, etc.
These findings do raise many questions that require further investigation. It is particularly important to be certain that the antigenic components identified in these lesions are really completely specific for C pneumoniae and not due to the lipid-altering capacity to change normal tissue antigenicity and that they do not represent the identification of a diseased tissue component that develops during atherosclerosis and that shares a common antigen with C pneumoniae. We have seen some evidence of this phenomenon in our studies of the immune mechanism in the pathogenesis of atheroarteritis in the monkey. Similar problems of the multiple origins of antigenic substances have plagued the investigation of rheumatic fever and several other mesenchymal diseases.
The development of additional DNA evidence should be actively pursued because the intriguing possibilities of these results pose important questions regarding the pathogenesis of the most prevalent debilitating and lethal disease in the United States.
The opinions expressed in this editorial are not necessarily those of the editor or of the American Heart Association.
- Copyright © 1995 by American Heart Association