These rare mutations in a human gene called TLR4 lend susceptibility to meningococcal sepsis, which strikes over 2,500 people a year in the United States. About half of those who contract meningococcal sepsis are younger than the age of two, and the disease has an overall case fatality rate of 12 percent.
"It's a very fast-moving, dramatic, and often fatal disease," says TSRI Immunology Professor Bruce Beutler, who led the research, which will be published in an upcoming issue of the journal Proceedings of the National Academy of Sciences.
"We took a large number of people with meningococcal sepsis and compared them to normal controls who were ethnically and geographically matched," says Beutler. "We found that the TLR4 gene had more mutations in the sepsis populations."
Besides demonstrating that the risk of severe sepsis increases with these mutations, which can be passed from parent to child, the study also suggests that it may be possible to protect people who are at risk. While not practical at the moment, eventually patients with mutations to their TLR4 genes might be given prophylactic treatment, for instance, before they undergo surgery or travel somewhere they are likely to be exposed to meningococcal bacteria.
Blinding the Immune System
Scientists had suspected that genetic factors determine who gets the severe form of the disease and who does not. Evidence for this was seen during outbreaks of this disease, when the severe and deadly form of sepsis was more likely to strike related individuals.
Further evidence was seen in mice, and it was known for years that certain strains of mice are more susceptible to infections with bacteria like N. meningitides--but nobody had ever shown th
Contact: Jason Bardi
Scripps Research Institute