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Serendipity leads to lifesaving discovery
Date:5/11/2011

About two years ago, Dr. Philippe Gros, a McGill University professor in the Department of Biochemistry and a Principal Investigator in thd McGill Life Sciences Complex, described a mouse mutant that was immunodeficient and hypersensitive to the Bacille Calmette-Gurin (BCG) vaccine and to tuberculosis (TB). In this model, Gros's team had found that the immunodeficiency was caused by a mutation in a regulatory protein of the immune system named IRF8.

A year later, a physician in Newcastle who had heard about Gros's work, contacted him about a three-month-old patient who was gravely ill and dying. The infant was suffering from an infection following a perinatal BCG vaccination. She had been treated aggressively with antibiotics but relapsed with additional infections. In addition, she showed a complete absence of circulating monocytes and dendritic cells in her blood two critically important types of immune cells. She was admitted into an ICU and it seemed nothing could be done to save her.

The clinical aspects of the infant's immuno-deficiency were so strikingly similar to those of Gros's earlier mouse model findings, that his research team investigated the human IRF8 gene for the presence of mutations in this infant. Dr. Gros group also examined IRF8 in a number of additional clinical cases of disseminated BCG infection following vaccination.

What they found were two distinct disease-causing mutations one that causes the severe reaction seen in the infant (autosomal recessive) and requires stem cell transplantation, and the other that causes a milder form of disease (autosomal dominant).

These findings, recently published in the New England Journal of Medicine, point to a critical role for IRF8 in the development and function of monocytes and dendritic cells and in protecting against mycobacterial infections like TB in humans.

According to Gros, the best part of this story is that the infant received th
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Contact: Allison Flynn
allison.j.flynn@mcgill.ca
514-398-7698
McGill University
Source:Eurekalert

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