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Forensics of the Immune System

March 13th, 2007 Medgadget Editors Genetics, Pediatrics

Researchers from the UT Southwestern Medical Center developed a new method to identify viruses and bacteria responsible for the most common acute infections in children, by looking at “fingerprints” that these infectious agents leave by way of the immune system:

“We are genetically programmed to respond differently to different infections. We have developed the tools to understand that,” said Dr. Octavio Ramilo, professor of pediatrics at UT Southwestern and lead author of a study appearing in the March edition of the journal Blood…
Different viruses and bacteria trigger the activation of very specific genes that code for proteins called receptors in leukocytes, the white blood cells th at help the body fight infections. Researchers surmised that if they looked at the leukocytes, they could detect the specific pattern of receptors — similar to a disease “fingerprint” — and be able to identify which infection was present. The process to identify such biosignatures is called gene expression profiling, and it’s done using microarray analysis.
Researchers extracted genetic material called RNA from a drop of blood and placed it on a special gene chip called a microarray, which contains probes for the whole human genome and measures which genes are turned on or off.
In this study, researchers analyzed gene expression patterns in leukocytes from 29 children at Children’s known to have one of four common infections: flu (influenza A); staph (Staphylococcus aureus); strep (Streptococcus pneumoniae); or E. coli (Escherichia coli).
They analyzed 35 genes that help distinguish infections and identified infectious agents with better-than-average success rates. Doctors were able to distinguish between the influenza, E. coli and strep infections in 95 percent of cases. A different set of genes distinguished E. coli from staph infections with 85 percent accuracy. Further investigation demonstrated clear distinction between viral and bacterial pneumonias.
The next step will be to study whether the microarray analysis can be applied in a more challenging clinical setting, such as an emergency room.
“When a child comes in with a fever to the ER, we want to see if we can predict who just has a virus and can go home, and who has to be admitted and put into the intensive care unit and treated with antibiotics. That’s our goal,” said Dr. Ramilo. “This is just the first step. But it establishes a basis for us to do that.”
While pediatricians couldn’t perform the analysis in their offices, researchers are already thinking about a possible way they could send in the results from the chip and get the analysis back via the Internet, for example.
“Pediatricians understand that this could change the way we do things,” said Dr. Ramilo, who leads pediatric infectious disease research at UT Southwestern and Children’s.
It could also prove useful for identifying previously unknown illnesses or biological weapons.
“Even if we don’t know which pathogen it is, we still can tell which family or which group it’s in, so if someone engineers a virus that has never been seen, we will have hints that it’s close to something that is known,” he said.

Press release…

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