Serendipity leads to lifesaving discovery

McGill research team recently published new findings in the New England Journal of Medicine, pointing 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.

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-Guérin (BCG) vaccine and to tuberculosis (). 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 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 , point to a critical role for IRF8 in the development and function of monocytes and and in protecting against mycobacterial infections like TB in humans.

According to Gros, the best part of this story is that the infant received the much needed stem cell transplant that ultimately cured her. Based on the team's research, her doctors were going to transplant her with one of the parents' cells as they were found to be a perfect match. However, when the team learned that the father was carrying one copy of the dysfunctional gene, and knowing that such a situation is deleterious in mice, the physicians opted instead to graft her with an unrelated donor.

"I think this is a great example of the 'discovery pipeline' we have tried to set up at the Complex Traits Group lab," said Gros. "This began as basic research. It evolved from genetic discoveries in mouse models through to validation in humans and knowledge translation to a positive clinical outcome."

"This is archetypal translational research," said Dr. Richard I. Levin, Vice-Principal of Health Affairs and Dean of Medicine at McGill. "When results from lab work conducted in the Complex can be shared across the ocean in context and in time to save a child's life, we know our objectives are being fulfilled."

Related Stories

TB breakthrough could lead to stronger vaccine

date Mar 03, 2009

A breakthrough strategy to improve the effectiveness of the only tuberculosis vaccine approved for humans provided superior protection against the deadly disease in a pre-clinical test, report scientists at The University ...

Tuberculosis vaccine passes phase I trial

date Mar 24, 2011

(PhysOrg.com) -- The currently available tuberculosis vaccine BCG is over 90 years old – and its effectiveness is declining. An increasing number of mycobacterial strains are emerging, against which the ...

New origin found for a critical immune response

date Mar 01, 2009

An immune system response that is critical to the first stages of fighting off viruses and harmful bacteria comes from an entirely different direction than most scientists had thought, according to a finding by researchers ...

Trials begin for 'essential' new TB vaccine

date Jul 30, 2007

Clinical trials are underway with the first new vaccine against TB in over 80 years. If successful, the tests will have major implications for TB control and could lead to the development of a new vaccine ...

Recommended for you

Breathless: How blood-oxygen levels regulate air intake

date 9 hours ago

Researchers have unraveled the elusive process by which small, highly vascular clusters of sensory cells in the carotid arteries "taste the blood," as a 1926 essay put it—the initial step in regulating ...

Sex matters ... even for liver cells

date 11 hours ago

Female liver cells, and in particular those in menopaused women, are more susceptible to adverse effects of drugs than their male counterparts, according to new research carried out by the JRC. It is well ...

Caring for blindness: A new protein in sight?

date 12 hours ago

Vasoproliferative ocular diseases are responsible for sight loss in millions of people in the industrialised countries. Many patients do not currently respond to the treatment offered, which targets a specific ...

When genes are expressed in reverse

date 12 hours ago

Genes usually always be expressed as in Western writing: from left to right on the white canvas of our DNA. So when we speak of the activity of our genome, in fact we are referring to the expression of genes ...

Technique could speed biologic drugs

date 17 hours ago

Antibodies are specific molecules that can lock onto a particular cellular structure to start, stop or otherwise temper a biological process. Because they are so specific, antibodies are at the forefront ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.