ABSTRACT
The presence of C pneumoniae IgA, IgG, or IgM in the serum generally reflects recurrence/persistence, chronic/past, or acute infection, respectively.5,12,32 However, the exact roles and reliability of these immunoglobulins acting as surrogate markers of and their temporal relations to the actual underlying infection remain unclear.5,12,32 An elevated antibody titre may simply reflect antigenic cross-reactivity rather than true underlying C pneumoniae infection.35 Individuals’ antibody responses to C pneumoniae infection may fluctuate over time or may even be variable due to different infective mode, dose, or history of past exposure.12,32,36 The extent of C pneumoniae found in tissue has been shown to correlate poorly with its serological marker.37,38 Newer diagnostic technique, such as the detection of C pneumoniae DNA by polymerase chain reaction (PCR) in circulating monocytes, may prove to be a more accurate surrogate marker of underlying vascular tissue infection.39,40
The lack of standardization in Chlamydia serology had made comparison of different seroepidemiological studies difficult, as they have often used different cut-off titres to define serpositivity.5,12,32 Owing to their inherent limitations in Chlamydia serological methods, positive seroepidemiological studies at best may only imply a genuine association rather than a causative link.12 On the contrary, negative seroepidemiological studies do not disprove a potential causative role of C pneu-
The detection of C pneumoniae at autopsy in atherosclerotic lesions of the coronary arteries, using electron microscopy (EM), was first reported by Shor and colleagues in 1992 (Fig. 7.1).41,42 More than 30 pathological studies have since demonstrated C pneumoniae (DNA, protein, and elementary body) in a wide variety of arterial specimens (coronary, carotid, aorta, femoral, popliteal and occluded bypass grafts). A variety of techniques such as immunocytochemistry (ICC), polymerase chain reaction (PCR) (Fig. 7.2),43 and electron microscopy (EM) have been used in these studies. The rate of C pneumoniae detection was about 60% in atherosclerotic lesions, versus 3% in control arterial tissues.44 Perhaps of greater relevance, ‘live’, viable C pneumoniae have now been cultured from coronary atherosclerotic specimens.45,46
Reflecting its ubiquitous presence, Chlamydia pneumoniae has also been found in human non-cardiovascular tissues such as lung, liver, spleen, bone marrow, lymph node, and granulomatous specimens.37 The mere presence of C pneumoniae in atherosclerotic lesions does not necessarily infer a direct pathogenetic role. The ‘innocent bystander’ hypothesis supports the notion that C pneumoniae could merely be carried by circulatory monocytes from the site of infection to remain dormant in atheromatous tissues.12,37 Jackson et al reported that C pneumoniae could be detected from a series of tissues removed from 38 autopsy cases at a rate of 29%–50% in cardiovascular tissues versus 5%–13% in non-cardiovascular tissues, and 9% in 33 granulomatous specimens (Table 7.2).37 Such findings could be interpreted as
The EM, ICC and PCR methods used in histopathological studies do not always correlate consistently.5,12,37 Comparison of these studies among themselves and with seroepidemiological studies is therefore hampered. A standardized histopathological technique may help to resolve this.
