Chlamydia & Multiple Sclerosis

Chronic Intrathecal ImmunoGlobulin (Ig) production is a hallmark of Multiple Sclerosis characterized by the presence of OligoClonal IgGs.

And, in addition, polyspecific recognition of different pathogens such as Measles, Rubella and Herpes Zoster Virus.

While the Antigen specificity of the OligoClonal IgGs in Multiple Sclerosis is largely unknown, the OligoClonal IgGs arising during CNS infectious diseases are reactive against the specific pathogen.

Recently, a link between Chlamydia Pneumoniae and Multiple Sclerosis has been claimed.

To test the possible role of C. Pneumoniae in Multiple Sclerosis, we analyzed:

1. Whether there is Intrathecal IgG production against C. Pneumoniae in Multiple Sclerosis and
2. If the OligoClonal IgGs in the CSF of Multiple Sclerosis patients recognize C. Pneumoniae

By studying paired Serum-CSF samples from 120 subjects (Definite Multiple Sclerosis , 46; Probable Multiple Sclerosis, 12; Other Inflammatory Neurological diseases, 35; Other Neurological Diseases, 27) by enzyme-linked immunosorbent assay.

We found that 24% of all patients with Definite Multiple Sclerosis.

But only 5% of patients with Other Inflammatory or Non-Inflammatory Diseases, produced IgGs specific for C. Pneumoniae Intrathecally (Definite Multiple Sclerosis versus Other Inflammatory Neurological Diseases: P = 0.027).

The presence of Intrathecal IgGs to C. Pneumoniae was independent of the duration of disease and relatively stable over time.

The major CSF OligoClonal IgG bands from Multiple Sclerosis patients with an Intrathecal Ig production to C. Pneumoniae.

Did not react towards purified elementary bodies and Reticulate bodies of C. Pneumoniae on affinity-mediated Immunoblot following IsoElectric Focusing (IEF-western blots).

In contrast, the IgGs in the CSF of control patients with NeuroBorreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi, by IEF-western blot analysis.

Concomitant analysis of the CSF of 23 patients with a nested polymerase chain reaction for C. Pneumoniae was negative in all cases.

Together, our findings strongly suggest that the Immune response to C. Pneumoniae is part of a polyspecific Intrathecal Ig production.

As is commonly observed with other pathogens. This argues against a specific role for C. Pneumoniae in Multiple Sclerosis.

Chlamydial DNA and viable organisms have been reported in the CerebroSpinal Fluid (CSF) of Multiple Sclerosis (MS) patients.

We investigated whether this phenomenon is specific for MS and not occurring in patients with Other Neurological Diseases (OND) or in healthy controls and whether it is caused by infected blood Monocytes having crossed the Blood-Brain Barrier.

Twelve (21%) of fifty-eight MS patients and 20 (43%) of 47 OND patients had Chlamydia Pneumoniae DNA in the CSF as determined by nested polymerase chain reaction.

Viable organisms were cultured from one OND patient. We failed to detect C. Pneumoniae in the CSF of 67 Neurologically healthy persons.

C. Pneumoniae was detected in parallel in the blood Monocytes of 2 of 6 CSF-positive MS patients and in 8 of 10 CSF-positive OND patients.

Thus, Chlamydial presence cannot exclusively be explained as being caused by contaminating infected Monocytes that have crossed the Blood-Brain Barrier.

In Peripheral Blood MonoNuclear Cell-negative patients, Chlamydia have been cleared from the circulation but persist in the Central Nervous System (CNS), indicating the establishment of a chronic process.

In summary, the presence of C. Pneumoniae in patients with Neurological Diseases is a common phenomenon and is not restricted to MS patients.

The PathoGenetic relevance of a chronic Chlamydial CNS infection for Neurological Diseases remains unclear, but the hypothesis that susceptible patients may be impaired in their ability to clear Chlamydiae from the CNS requires further examination.

Chlamydia Pneumoniae is a common respiratory pathogen that is now being implicated in a number of chronic diseases.

That the organism can infect Vascular Endothelium, Macrophages and smooth muscle cells suggests that it may play a role in many Systemic Diseases. The present review focuses on the possibility that the Central Nervous System can also be a target of this agent.

The tropism of C. Pneumoniae to the Neural tissue suggests it may play a role in diverse Neurologic Diseases, Including Alzheimer's Disease, Multiple Sclerosis and Giant-Cell Arteritis.

Since current studies indicate the possible involvement of Chlamydia Pneumoniae in the PathoGenesis of Multiple Sclerosis (MS), demonstration of C. Pneumoniae in the CerebroSpinal Fluid (CSF) of patients with MS is highly desirable.

However, there is controversy concerning the detection of C. Pneumoniae in CSFs from MS patients due to the lack of a standard protocol for extraction and detection of C. Pneumoniae DNA.

In this regard, we attempted to establish a highly effective extraction protocol for C. Pneumoniae DNA from CSFs utilizing a commercial kit and a PCR detection method.

The extraction and PCR detection protocol established in this study succeeded in detecting as few as 20 C. Pneumoniae organisms in 200 &mgr;l of mock CSF.

The use of this protocol to detect C. Pneumoniae DNA in CSFs revealed that 68% of CSF samples obtained from patients with MS were positive (11 out of 16 samples) for Chlamydia DNA.

Thus, the protocol established here is sensitive enough to detect Chlamydia DNA from CSFs and can be used by other laboratories for evaluation of the presence of Chlamydiae in CSFs because the protocol is based on the use of a commercial kit.

The cause of Multiple Sclerosis (MS) is unknown. Despite indications from Epidemiological and identical-twin studies that MS is infectious, no Virus or other infectious agent has been tightly linked to disease.

The isolation of Chlamydia Pneumoniae from the CerebroSpinal Fluid (CSF) of MS patients and the detection of both Chlamydia-specific DNA and AntiBody in MS CSF have been reported.

Other analyzes of Brain and CSF have shown no significant difference in C. Pneumoniae-specific DNA or AntiBody between MS and control subjects.

Recent work has revealed Intrathecal production of C. Pneumoniae-specific IgG in only 24% of MS patients compared with 5% of control patients. More importantly, the major CSF OligoClonal Bands from MS patients did not react to C. Pneumoniae.

We investigated the presence of Chlamydia Pneumoniae in 81 normal and pathological specimens obtained from postmortem Brain tissues of patients with Multiple Sclerosis and with Other Neurological or NonNeurological Diseases.

The assays used included PCR amplification of all DNA samples in the initial study. Culture and a second PCR amplification of the organism in a subset of 19 Brain specimens were also performed in two separate laboratories.

All results were negative. Thus, this study on a large number of Brain tissues suggests that C. Pneumoniae is not involved in inflammatory DeMyelination.

Our identification of Chlamydia Pneumoniae in the CerebroSpinal Fluid (CSF) of a patient with Multiple Sclerosis (MS) led us to examine the incidence of this organism in the CSF.

From 17 patients with Relapsing/Remitting MS, 20 patients with Progressive MS, and 27 patients with Other Neurological Diseases (OND).

CSF samples were examined for Chlamydia Pneumoniae by culture, polymerase chain reaction assays, and CSF ImmunoGlobulin (Ig) reactivity with Chlamydia Pneumoniae elementary body Antigens.

Chlamydia Pneumoniae was isolated from CSF in 64% of MS patients versus 11% of OND controls.

Polymerase chain reaction assays demonstrated the presence of Chlamydia Pneumoniae MOMP Gene in the CSF of 97% of MS patients versus 18% of OND controls.

Finally, 86% of MS patients had increased CSF AntiBodies to Chlamydia Pneumoniae elementary body Antigens.

As shown by enzyme-linked Immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls.

The specificity of this AntiBody response was confirmed by western blot assays of the CSF, using elementary body Antigens.

Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic AntiBodies against Chlamydia Pneumoniae.

Infection of the Central Nervous System with Chlamydia Pneumoniae is a frequent occurrence in MS patients.

Although the organism could represent the PathoGenetic agent of MS, it may simply represent a secondary infection of damaged Central Nervous System tissue.

A therapeutic trial directed at eliminating Chlamydia Pneumoniae from the Central Nervous System may provide additional information on its role in MS.

Comments:

Ann Neurol 1999 Jul;46(1):4-5

Multiple Sclerosis is an acquired disease of the Central Nervous System, probably due to a transmissible factor, and characterized by pathological changes in the White Matter of the Brain and Cord.

These changes consist of loss of the Myelin covering of the Axons in the form of DeMyelinative plaques.

Based on a review of studies, Chlamydia may indeed be one of the agents involved in the PathoPhysiology of Multiple Sclerosis.