Researchers at Johns Hopkins have discovered a single molecule that is a cause of an autoimmune disease in the central nervous system, called transverse myelitis ( TM ), that is related to multiple sclerosis.

In a study published in the The Journal of Clinical Investigation, Adam Kaplin, at The Johns Hopkins University School of Medicine, and Douglas Kerr, at Hopkins, showed that the levels of the protein, IL-6, are dramatically elevated in the spinal fluid of transverse myelitis patients.

Although the majority of transverse myelitis patients suffer a single attack, 15 percent to 30 percent of patients go on to develop full-blown multiple sclerosis.
Transverse myelitis evolves rapidly and without warning and usually results in permanent impairment, including weakness of the legs and arms, bowel and bladder dysfunction, pain and paralysis.

IL-6 is a chemical messenger that cells of the immune system use to communicate with one another. One of the cell types injured by high levels of IL-6 includes oligodendrocytes, which help produce the protective myelin sheath coating around nerve cells.
The findings offer one possible mechanism responsible for demyelinating disorders, such as transverse myelitis and multiple sclerosis, and may aid in the development of effective therapies against these disorders, the researchers say.

" This is the first time a single culprit has been identified as causing a CNS autoimmune disease," said Kaplin.

The researchers began investigating the protein IL-6 when they became aware that transverse myelitis patients suffered from memory impairment and depression. IL-6 has been implicated in mood and concentration disorders.

" This discovery is a success story that begins with listening carefully to what patients are telling us about their suffering and then collaborating across disciplines to open up new avenues of investigation," said Kaplin.

" Transverse myelitis is related to other autoimmune disorders of the nervous system, including Guillain-Barré syndrome, multiple sclerosis and acute disseminated encephalomyelitis. This study may give us a foothold in understanding all of these disorders and how they are linked together. The benefit is, therefore, not only to those who are paralyzed by transverse myelitis, but to those who have disabilities due to a variety of autoimmune disorders. We are actively using these findings to aid in developing future diagnostic, prognostic and therapeutic advancements," said Kerr, director of the Johns Hopkins Transverse Myelitis Center, the only center devoted to transverse myelitis in the world.

Researchers analyzed 42 inflammatory proteins in the cerebrospinal fluid of both transverse myelitis and healthy patients. They found that IL-6 was consistently elevated in transverse myelitis patients' spinal fluid. Further, the level of IL-6 directly correlated with the severity of paralysis.

Using cell culture and animal studies, the researchers confirmed that elevated IL-6 levels were directly injurious to the spinal cord. They showed that spinal fluid from transverse myelitis patients induced death of spinal cord cells when cultured in a dish and that IL-6, when infused in adult rats, induced paralysis. Under the microscope, tissue from IL-6-infused rats showed demyelination and injury of axons, pathology that was nearly identical to that seen in human patients with transverse myelitis.

Kerr and Kaplin also deduced that the reason IL-6 elevations injure only the spinal cord and not other regions of the nervous system was because distinct regions of the nervous system have different responses to IL-6. They concluded that these different types of responses might be a part of why different autoimmune disorders of the nervous system affect distinct regions and cause distinct symptoms.

Source: Johns Hopkins Medical Institutions, 2005


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