Marca genómica en la sangre identifica infección viral subyacente

DURHAM, N.C. –Científicos han identificado una “marca” genómica en sangre circulante que revela la exposición a virus del tracto respiratorio superior, como los del resfriado y la influenza, aun antes de que los síntomas aparezcan.
La marca del identificador viral refleja una serie de cambios sutiles pero sólidos en los genes que son activados cuando el organismo responde a la infección. La señal de la “marca” es suficientemente fuerte en individuos sintomáticos como para revelar con certeza si su infección es viral o bacteriana. La “marca” también puede discriminar entre quién tiene una infección viral y quién no a partir de un simple tubo de sangre.
“Este trabajo está aun en una relativamente temprana fase de descubrimiento, pero somos optimistas de que estos hallazgos puedan conllevar a una forma totalmente novedosa de diagnosticar enfermedades infecciosas”, dijo Geoffrey Ginsburg, M.D., Ph.D.,, director del Duke University’s Center for Genomic Medicine en el Institute for Genome Sciences & Policy y autor principal del estudio que aparece en la revista Cell Host & Microbe.
http://www.eurekalert.org/pub_releases/2009-08/dumc-gsi073009.php

Researchers say the discovery could lead to dramatic changes in the way doctors care for the millions of people who develop upper respiratory infections every year. Ginsburg says the symptoms of a cold, the flu or pneumonia can appear similar, but right now, doctors can’t tell what the patient really has until laboratory tests are conducted, and that can take days.
“Until results are in, treatment is pretty much a best guess. Knowing exactly which pathogen is involved is important because it affects the urgency of response and the type of treatment,” says Ginsburg. “This approach could lead to more precise, informed and tailored therapy – essentially, personalized care for infectious disease. That’s better for the patient and better for public health, in general.”
Christopher Woods, M.D., an associate professor of medicine at Duke and the Chief of the Infectious Disease Section at the Durham Veterans Administration Medical Center, says a quick test to determine the real cause of disease has other benefits, too. “It could mean more appropriate use of antibiotics. Overuse of antibiotics can lead to the emergence of drug-resistant pathogens, and no one wants to see more of that.”
The discovery is based upon the fact that the body’s immune system starts responding very quickly and in a highly specific manner when exposed to a viral pathogen as opposed to a bacterial one. “A detailed reading of that response, using gene expression data, reveals what type of pathogen the person is reacting to,” says Aimee Zaas, M.D., M.H.S., an infectious diseases physician at Duke and the lead author of the study.
Zaas and colleagues recruited 57 healthy volunteers who agreed to be inoculated with either a live cold virus (rhinovirus), the respiratory syncytial virus, or the influenza A virus. Researchers first took detailed baseline measures of genomic profiles in participants’ blood, nasal fluid, breath and urine, and then inoculated the volunteers with one of the three viruses. They waited to see who became sick, and noted when symptoms first appeared, measuring markers of biological response at multiple time points after exposure. Volunteers were quarantined during the time they were infectious.
The research team studied changes in gene expression patterns in the participants’ blood and identified 30 genes – many of which were already known to be active in the body’s response to viral infections – whose expression patterns changed only among those who became symptomatic.
Investigators tested this “acute respiratory viral signature” in an independently acquired data set of gene expression patterns among people infected with influenza A and found that the signature was able to clearly distinguish with 100 percent accuracy between individuals who were infected and those who were not.
“We believe there will be multiple applications for this discovery,” says Ginsburg. “This is simply the first step. Right now we are replicating our results in additional studies and also trying to validate these expression patterns in additional studies. We want to be careful and not draw any conclusions too quickly. Even though the signature we identified appears to be an excellent diagnostic, there may be other genes that can make it even better.”
The researchers say the acute viral response signature may be applicable only to people who have healthy immune systems. “We would need to show that this approach also works in patients with underlying immune deficiencies before we could offer it as a potential diagnostic tool for everyone,” says Zaas.