The infection connection  pg. 2

One bacterial virulence factor Peek and colleagues have identified is a group of linked genes called the cag island. Bacteria that express cag genes are able to trigger the production of inflammatory cytokines by gastric epithelial cells.

“Persons who have certain polymorphisms in cytokine genes can produce increased amounts of these molecules in response to the bacterial infection,” Peek says. This causes an enhanced inflammatory response, which is thought to be the direct cause of gastric ulcers.

This combination—of a highly virulent bacterium and a host that overreacts to the infection—might be the answer to this vexing problem.

While identifying the infectious agent responsible for ulcers and gastric cancer was relatively easy (because H. pylori is virtually the only bacterial species that can colonize the normal stomach), the picture gets much cloudier when dealing with other tissues. For example, Peek describes, “in the large bowel, there are approximately 1012 (one trillion) bacteria per gram of tissue, so trying to pinpoint one species that causes a chronic inflammatory disorder that affects this organ, such as Inflammatory Bowel Disease (IBD), is prohibitive.”

Finding the cause of inflammatory neurodegenerative diseases like Alzheimer’s disease, multiple sclerosis (MS) and the myasthenias (which cause muscle weakness) is hampered by the long time course—often 20 years—from the onset of disease to severe disability.

MS is a progressive demyelinating disease with periodic relapses and remissions in which the protective myelin around the nerves is destroyed or damaged, resulting in a range of neurological symptoms.

Although the cause is unknown, MS has been classified as an “autoimmune” disease in which the immune system mistakenly attacks body tissues that bear an auto-antigen it recognizes as foreign. For some diseases, like the myasthenias, an auto-antigen has been identified. But, so far, no convincing auto-antigen has been found for MS.

“The inference that an inflammatory disease is autoimmune is largely by default since we are unable to find an infectious agent,” says Subramanian Sriram, M.D., professor of Neurology, and Microbiology & Immunology at Vanderbilt.

Just because scientists haven’t found a causative organism(s) doesn’t mean it doesn’t exist, however. “We may have overlooked them,” Sriram says. “To use the cliché, ‘absence of evidence is not evidence of absence.’”

Both a virus (Human Herpesvirus 6) and a bacterium (Chlamydia pneumoniae) have been proposed as inciting silent infections that may underlie MS. However, no definitive link has yet been shown for either of these candidates.

Although at least five labs, including Sriram’s, have found C. pneumoniae in the spinal fluid of MS patients, several others have not. While he thinks that the bacterium definitely plays a role in the disease, the nature of MS makes the link difficult to establish.

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