Winter 2002 - Volume 13, No. 1
Graduate School Alumni Profile
Bacterial Genomics Reveals MS Trigger
Infection with a common bacteria could be the switch that turns on the autoimmune response in multiple sclerosis (MS) according to the findings of Wayne State University PhD graduate, Derek Lenz, now of the Scripps Research Institute in La Jolla, Calif. He described the work he carried out as part of Robert Swanborg’s team at Wayne State University School of Medicine. He said studies in rats show that an antigen found in the bacteria Chlamydia pneumoniae mimics part of a myelin protein in the animal’s central nervous system. When injected into the animal, it provokes the immune response that causes the rodent version of MS, experimental allergic encephalitis.
Scientists have theorized for years that MS might be caused by an infectious agent, according to Dr. Lenz. An early suspect was the measles virus, but it was impossible to use the virus to precipitate out the aggregations of auto-antibodies, known as oligoclonal bands, typically found in the cerebrospinal fluid of MS patients. “So that idea kind of went by the board,” he said.
But there was strong evidence from epidemiological data that an infection was involved at some stage. An outbreak of MS in the Faroe Island occurred shortly after World War II – “that strongly suggests that the troops brought some sort of pathogen with them,” Dr. Lenz said.
Lenz’s colleague, Alan Hudson, analyzed the pattern of the main outbreak and three subsequent outbreaks of gradually decreasing severity. He found that the events fitted exactly the pattern of C. pneumoniae infection in the population. “He tried every way possible, but there was no way that he couldn’t make them fit,” Dr. Lenz recalled.
However, C. pneumoniae may seem an unlikely cause of MS – it is a ubiquitous pathogen and, by the age of 70, nearly everybody will show a positive blood test. It causes silent epidemics of bronchitis and low-grade respiratory infections. When not infecting the cells of the lungs, it survives as a spore that is metabolically inert and almost impossible to destroy.
Yet, evidence that the bacteria cold be involved in the disease came from the Subramaniam Sriram’s team at the Vanderbilt University Multiple Sclerosis Center in Nashville, Tenn. He previously reported that 97 percent of MS patients had evidence of C. pneumoniae infection in the central nervous system, compared with only 16 percent in patients with other neurological diseases.
More importantly, Chlamydia antigens precipitated out of the oligoclonal bands. “That’s an amazing result – nobody had been able to do that before and the existence of these bands has been known about for more than 60 years,” Dr. Lenz said.
Now Dr. Lenz and his colleagues have taken the work a stage further. By searching through the chlamydial genome, they found a region coding for a protein fragment that closely resembled the MBP 68-86 region of the myelin protein known to be the main target in EAE. Both peptides were found to activate the T cells that stimulate the encephalitis response, and affected rats showed similar signs of disease.
Dr. Lenz accepts that infection is not the whole story, as there is strong evidence for a genetic component to MS. Women originating from Northern Europe have an exceptionally high incidence, and Seattle and Minneapolis - two US cities with large populations of Scandinavian immigrants - are both disease hot spots, he says.
Nor is it likely that C. pneumoniae is the only infection that can provoke the inflammation that leads to MS. "I don't necessarily think that Chlamydia is the sole etiological agent - I would say that the disease process is the end of many different beginnings," Dr. Lenz concluded.
Article source: BioMedNet.com