Trade off. Brazilian children with the greatest resistance to infection by parasitic worms seem to be also the most susceptible to asthma.
Kathleen Barnes
WASHINGTON, D.C. .- Parasites get a bad reputation for a reason. They cause a litany of diseases with terrifying crowd of symptoms. But increasing evidence suggest that they may also prevent disease. And now there is genetic evidence to suggest that this is true. New research presented here yesterday at the annual meeting of the American Association for the Advancement of Science (which publishes Science NOW) finds that a gene associated with increased risk of asthma is also related to resistance against a parasitic worm.
scientists have long suspected that allergies and asthma common in the developed and relatively rare in poor countries, are the result of a lack of exposure to microbes. This 2-decade-old idea, called the hygiene hypothesis, suggests that lack of exposure to dangerous parasites in childhood makes the adaptive arm of the immune system more likely to overreact when he contacts benign allergens.
Kathleen Barnes, an expert anthropologist and genetics at Johns Hopkins University in Baltimore, Maryland, and colleagues investigated the relationship between asthma and particular parasitic worm, Schistosoma mansoni Conde, a group of fishing rural villages on the coast of Brazil. The worm is common in the area, and up to 85% of residents are exposed.
Previous studies have shown that in areas such as Conde, where parasitic worms are endemic, individuals who produce the most helical gear-specific antibodies in particular, an antibody called IgE, which triggers inflammation tend to be more resistant to worm infection. According to research by Barnes, the resistance appears to be about 30% heritable.
The researchers noted that after they administered drugs to rid the people of Conde worms, the incidence of asthma and allergy symptoms increases. So Barnes hypothesized that mutations that help people repel parasitic worms might be the same mutations that make them susceptible to asthma and allergies. If an individual product lots of IgE in response to a worm, he or she might also produce a lot of IgE in response to an allergen.
The team collected blood samples and 850 people in Condé stool. They tested their blood for antibodies against the worm to measure their immune response and searched their stool for worm eggs to determine how they were heavily infected. The researchers decided to focus on genes that have been linked to asthma risk. They were particularly interested in IL-33 , a gene linked to inflammation which is overexpressed in lung tissue of asthma compared with people without the disease. " IL-33 stands as a stronger candidate genes for asthma to date," says Barnes.
Barnes and colleagues selected 23 genetic markers across the gene and tested whether any of them were associated with the worm resistance in people of Conde. Five of them have shown a strong association, and those who happened to be the exact same markers that are associated with asthma. "And what we are most excited is that the relationship is reversed," said Barnes. "Thus, [gene variant] that confer risk for asthma confers protection against [worm infection]."
The researchers postulate that natural selection may favor mutations that protect against infection by the worm and that these same mutations could inadvertently increase the risk of other diseases such as asthma. Researchers have not yet found the exact mutation responsible for worm resistance and asthma susceptibility. To find it, they will have "to drill deeper down," said Barnes. She speculates that the culprit may be a mutation in a region of the genome that regulates the activity of IL-33 gene.
Jennifer Ingram, a cell biologist who studies asthma at Duke University in Durham, North Carolina, said the finding that deworming drugs increased the incidence of asthma symptoms is " striking. "she added that the work of Barnes is important because it highlights the field to the molecular mechanisms that may contribute to asthma.
David Van Sickle, a medical anthropologist at the University of Wisconsin, Madison, who presented during the same session as Barnes points out that global estimates of asthma prevalence are based largely on asking people if a doctor has ever told they have asthma. But diagnoses vary from culture to culture. Van Sickle has found, for instance, that doctors in India are much less likely than doctors in Wisconsin to diagnose a person with clear symptoms of asthma with the disease. So the true prevalence of asthma in India or other countries could be higher or lower than current estimates. Changes in the prevalence of asthma would not necessarily negate the hygiene hypothesis, he said, they could complicate the situation. However, he said the work of Barnes is "elegant".
Follow our complete coverage of the 2011 AAAS
0 Komentar