Other chronic diseases & C. pneumoniae
Multiple sclerosis (MS) is a chronic inflammatory condition characterised by demyelination of the central nervous system. Classically, demyelinated plaques are distributed in both time and space. The cause is unknown, but one theory is that disease is produced by the host immune response to an infectious agent or to autoantigen [lay reader: a component of one's self to which the immune system aberrantly reacts]. Viruses have most often been implicated as potential agents of MS, but as long ago as 1983 it has been hypothesized that Chlamydia might play a role [Perlmutter & Darvish, 1983]. In 1998 a case report described the detection of C. pneumoniae by culture and PCR [DNA detection] in the cerebrospinal fluid (CSF) of a patient with MS whose condition improved with antibiotics [Sriram et al., 1998]. Subsequently, the same group found that C. pneumoniae could be cultured from the CSF in 64% of 37 patients with MS and in 11% of patients with other neurological diseases. For C. pneumoniae DNA the corresponding figures were an astonishing 97% versus 18% respectively [Sriram et al., 1999]. Immunoelectrophoresis of the CSF in MS often shows oligoclonal bands [lay reader: separation of the proteins of the CSF in an electric field, which in MS reveals characteristic patterns] and in a third study, this group demonstrated that in 16 of 17 MS patients, the oligoclonal bands reacted against C. pneumoniae elementary body antigens compared with none of 14 control patients [Yao et al., 2001]. The authors cautiously concluded that, although the organism could represent the trigger for MS, it might simply represent secondary infection of damaged central nervous system tissue.
A German study confirmed that C. pneumoniae was found preferentially in the CSF of MS patients, although at lower levels [Layh-Schmitt et al., 2000]. Another German group found C. pneumoniae DNA in 12/58 (21%) of MS patients; in 20/47 (43%) of patients with other neurological diseases and in 0/67 neurologically healthy persons. The presence of the Chlamydiae was not simply explained by the presence of C. pneumoniae-infected monocytes that had crossed the blood-brain barrier. In peripheral blood mononuclear cell-negative patients, Chlamydiae had been cleared from the circulation but persisted in the central nervous system, indicating an established chronic process [Gieffers et al., 2001]. Sotgiu et al., 2001 in Italy found C. pneumoniae DNA by PCR in the CSF 2 of 32 MS patients and in 0 of 30 neurological controls.
Interestingly a 20-mer peptide from a C. pneumoniae protein that shares a 7 amino acid motif with a critical epitope of myelin basic protein induced a Th1 cellular immune response accompanied by severe clinical and histological experimental autoimmune encephalomyelitis in Lewis rats. Further work is required to determine whether this is a chance phenomenon, as it may well be, or a critical pathological process for the natural disease [Lenz et al., 2001].
Swanborg et al., 2003 point out that there is good evidence for a possible infectious component in the development of multiple sclerosis and that more than 20 agents have been implicated. While recent evidence has particularly implicated C. pneumoniae and Herpes hominis 6 virus, (and also host possession of the APOE epsilon 4 allele), no conclusion is possible concerning the role of these organisms in multiple sclerosis.
[Comment: Although a number of studies have failed to detect C. pneumoniae in brain tissue or CSF [Hammerschlag et al., 2000; Boman et al., 2000; Numazaki & Chibar, 2001; Saiz et al., 2001], it seems that the presence of C. pneumoniae in patients with neurological diseases occurs and is not restricted to MS patients. Differences between individual study results are probably attributable to lack of methodological standardisation, particularly for PCR. As for heart disease, it is unclear whether the Chlamydiae cause the condition or are simply able to associate with damaged tissue. However, the hypothesis that susceptible patients may be impaired in their ability to clear Chlamydiae from the CNS [Gieffers et al., 2001] requires further examination. For a review of Chlamydiae in CNS infection see Yucesan & Sriram, 2001].
[MEW - August 2003]
NEXT: C. pneumoniae and Alzheimers disease
Boman, J., Roblin, P. M., Sundstrom, P., Sandstrom, M. & Hammerschlag, M. R. (2000). Failure to detect Chlamydia pneumoniae in the central nervous system of patients with MS. Neurology 54, 265 .
Gieffers, J., Pohl, D., Treib, J., Dittmann, R., Stephan, C., Klotz, K. et al. (2001). Presence of Chlamydia pneumoniae DNA in the cerebral spinal fluid is a common phenomenon in a variety of neurological diseases and not restricted to multiple sclerosis. Annals of Neurology 49, 585 - 589.
Hammerschlag, M. R., Ke, Z., Lu, F. M., Roblin, P., Boman, J. & Kalman, B. (2000). Is Chlamydia pneumoniae present in brain lesions of patients with multiple sclerosis? Journal of Clinical Microbiology 38, 4274 - 4276. Full text
Jr, H. M. & Sriram, S. (2001). An Infectious Basis for Multiple Sclerosis: Perspectives on the Role of Chlamydia pneumoniae and Other Agents. BioDrugs 15, 199 - 206.
Layh-Schmitt, G., Bendl, C., Hildt, U., Dong-Si, T., Juttler, E. & Schnitzler, P. et al. (2000). Evidence for infection with Chlamydia pneumoniae in a subgroup of patients with multiple sclerosis. Annals of Neurology 47, 652 - 655.
Lenz, D. C., Lu, L., Conant, S. B., Wolf, N. A., Gerard, H. C., Whittum-Hudson, J. A., Hudson, A. P. & Swanborg, R. H. (2001). A Chlamydia pneumoniae-specific peptide induces experimental autoimmune encephalomyelitis in rats. Journal of Immunology 167, 1803 - 1808.
Numazaki, K. & Chibar, S. (2001). Failure to detect Chlamydia pneumoniae in the central nervous system of patients with MS. Neurology 57, 746. [Letter]
Perlmutter, L. J. & Darvish, M. (1983). Possible relationship of Chlamydia to multiple sclerosis. Medical Hypotheses 12, 95 - 98.
Saiz, A., Marcos, M. A., Graus, F., Vidal, J. & Jimenez de Anta, M. T. (2001). No evidence of CNS infection with Chlamydia pneumoniae in patients with multiple sclerosis. Journal of Neurology 248, 617 - 618. Full letter
Sotgiu, S. et al., (2001). Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls. Multiple Sclerosis 7, 371 - 374.
Sriram, S., Mitchell, W. & Stratton, C. (1998). Multiple sclerosis associated with Chlamydia pneumoniae infection of the CNS. Neurology 50, 571 - 572.
Sriram, S., Stratton, C. W., Yao, S., Tharp, A., Ding, L., Bannan, J. D. et al. (1999). Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Annals of Neurology 46, 6 - 14.
Swanborg, R. H., Whittum-Hudson, J. A. & Hudson, AP. (2003). Infectious agents and multiple sclerosis--are Chlamydia pneumoniae and human herpes virus 6 involved? Journal of Neuroimmunology 136, 1 - 8.
Yao, S. Y., Stratton, C. W., Mitchell, W. M. & Sriram, S. (2001). CSF oligoclonal bands in MS include antibodies against Chlamydophila antigens. Neurology 56, 1168 - 1176.
Yucesan, C. & Sriram, S*. (2001). Chlamydia pneumoniae infection of the central nervous system. Current Opinions in Neurology 14, 355 - 359.