Dec. 3, 2009 Why do some people who are exposed to tuberculosis not become infected or develop the disease? Dr. Erwin Schurr and his team at the Research Institute from the McGill University Health Centre (RI-MUHC), in collaboration with Dr. Alexandre Alcais, from the Institut national de la santé et de la recherche médicale (INSERM) in Paris, has shed light on this question for the first time. Their results show that one or multiple genes might provide certain people with resistance to tuberculosis infection. Their findings are published in the Journal of Experimental Medicine.
Tuberculosis (TB) is an infectious disease caused by a bacterium called Mycobacterium tuberculosis (MTB). Two thirds of the world population are infected by this mycobacterium. Nevertheless, 20 per cent of people exposed to the mycobacterium are resistant to infection and can therefore, not develop the disease. " For our study, we were interested in this minority of people who live in high-exposure areas without becoming infected," said Dr. Schurr. "We tried to understand how these people develop resistance to TB infection."
Their findings show the existence of a chromosomal site, or a locus, that controls resistance to TB infection. Out of the 128 families studied, who come from an area in South Africa with high tuberculosis rates, after considering non genetic factors such as age, 20 per cent of individuals show natural resistance. "In other words, some people seem to have a particular genetic heritage that makes them naturally resistant to MTB infection," explained Dr. Alcais.
"The discovery of a genetic resistance factor is a major step forward in the fight against TB both locally and globally," said Dr. Schurr. This is a major development for people with HIV, for whom tuberculosis is a leading cause of mortality, as it is responsible for about 13% of AIDS-related deaths in the world. "Since they accelerate each other's progress, HIV and tuberculosis are partners in crime; if we can prevent infection, immune deficient patients will no longer be threatened by TB," stated Dr. Schurr.
"Right now, our challenge as researchers is to concentrate on identifying this genetic factor and its mechanisms that lead to resistance against TB infection," explained Dr. Alcais. The hope is that these genetic resistance factors can be used in the near future to prevent TB infection in the general population by stimulating the mechanism responsible for resistance.
"If we can make everyone resistant to tuberculosis infection, this major public health problem could be wiped off the map," concluded Dr. Schurr.
Dr. Erwin Schurr is a researcher at the Centre for the Study of Host Resistance at the Research Institue of the MUHC and a molecular geneticist at the Department of Human Genetics at the McGill Faculty of Medicine, McGill University
Dr. Alcais is a researcher at the Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, France, University Paris Descartes, Necker Medical School, France, Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, USA.
This study was funded by a grant from the Canadian Institutes for Health Research (CIHR), Sequella/AERAS Global Tuberculosis Vaccine Foundation, and the Gates Foundation. Some authors received financial support from Fonds de la recherche en santé du Québec (FRSQ).
The study was co-authored by Caroline Gallant, Leah Simkin and Erwin Schurr from RI MUHC, Aurelie Cobat from INSERM U550, Paris, France; Jean-Laurent Casanova, Laurent Abel and Alexandre Alcais from INSERM U550, Université Paris Descartes, Paris, France and Laboratory of Human Genetics, The Rockefeller University, NYC, U.S.A; Ann Boland-Auge, Centre National de Génotypage, Evry, France, Mark Doherty, Statens Serum Institute, Copenhagen, Danemark, Gillian Black, Kim Stanley, Paul van Helden and Eileen Hoal, Stellenbosch University, Tygerberg, South Africa, Jane Hughes, Brian Eley, and Willem Hanekom, University of Cape Town, Cape Town, South Africa.
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