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Multiple sclerosis-associated agent: transmission to animals and some properties of the agent
Abstract:
In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs. All of eight MD brains contained this agent at titers as high as 10(-9)/g of brain tissue. The agent was found in MS sera at titers up to 10(-3)/ml of serum, but its presence depended to some extent on the clinical status of the patients; it was observed more frequently in sera of patients with active disease (73%) thatn in sera of patients with quiescent disease (31%). Control brain tissues or sera failed to induce PMN depression. The apparently MS-associated agent (MSAA) passed through 50-nm but not 25-nm membrane filters (Millipore Corp.) and was largely sedimented at 105,000 X g but not at 50,000 X g for 1 h. It multiplied to high titers in the central nervous tissue of the inoculated animals and could be serially transmitted from animal to animal by passage of brain homeganates. Various observations and considerations appear to preclude that MS-associated agent represents an indigenous animal virus. Although its role in MS remains to be determined, it should be considered a candidate for the etiology of this disease.
Insights
Researchers found an agent in multiple sclerosis (MS) patients' brain tissue and sera that causes a temporary drop in white blood cells (polymorphonuclear leukocytes) in animals. This agent may be a candidate for causing MS.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Previous observations suggested the presence of an infectious agent in multiple sclerosis (MS).
- The agent's effect on polymorphonuclear leukocytes (PMN) was noted.
- The agent's presence and characteristics in MS patients required further investigation.
Purpose of the Study:
- To confirm and extend previous findings regarding an agent in MS patients.
- To investigate the agent's presence in brain tissue and sera of MS patients.
- To characterize the agent's biological and physical properties.
Main Methods:
- Inoculation of mice, rats, hamsters, and guinea pigs with brain tissue and sera from MS patients.
- Monitoring of PMN levels in inoculated animals.
- Filtration and ultracentrifugation to determine the agent's size and sedimentation properties.
- Serial transmission studies in animals.
Main Results:
- An agent inducing transitory PMN depression was detected in 8/8 MS brains and MS sera.
- The agent's titer was higher in MS brains (up to 10(-9)/g) than in sera (up to 10(-3)/ml).
- Agent presence in sera correlated with active MS disease (73% vs. 31% in quiescent disease).
- Control tissues/sera did not induce PMN depression.
- The agent passed 50-nm but not 25-nm filters and sedimented at 105,000 x g.
- The agent multiplied in animal central nervous tissue and was serially transmissible.
Conclusions:
- An MS-associated agent (MSAA) was identified in brain tissue and sera of MS patients.
- MSAA induces PMN depression in multiple animal species and replicates in animal CNS.
- MSAA is a candidate for the etiology of multiple sclerosis, though its role requires further determination.