Featured Research

from universities, journals, and other organizations

Serendipity leads to lifesaving discovery: Team finds disease-causing mutations and saves a baby girl

Date:
May 11, 2011
Source:
McGill University
Summary:
Recent findings 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 (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.

Related Articles


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 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 Life Sciences 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."

Other McGill researchers involved in this study are Sandra Salem (PhD candidate) and Drs. Albert Berghuis and Anny Fortin. The study involved a large collaboration between scientists and clinicians from The Rockefeller University in New York, L'Hopital Necker in Paris, Newcastle University and King's College in London.


Story Source:

The above story is based on materials provided by McGill University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sophie Hambleton, Sandra Salem, Jacinta Bustamante, Venetia Bigley, Stéphanie Boisson-Dupuis, Joana Azevedo, Anny Fortin, Muzlifah Haniffa, Lourdes Ceron-Gutierrez, Chris M. Bacon, Geetha Menon, Céline Trouillet, David McDonald, Peter Carey, Florent Ginhoux, Laia Alsina, Timothy J. Zumwalt, Xiao-Fei Kong, Dinakantha Kumararatne, Karina Butler, Marjorie Hubeau, Jacqueline Feinberg, Saleh Al-Muhsen, Andrew Cant, Laurent Abel, Damien Chaussabel, Rainer Doffinger, Eduardo Talesnik, Anete Grumach, Alberto Duarte, Katia Abarca, Dewton Moraes-Vasconcelos, David Burk, Albert Berghuis, Frédéric Geissmann, Matthew Collin, Jean-Laurent Casanova, Philippe Gros. IRF8 Mutations and Human Dendritic-Cell Immunodeficiency. New England Journal of Medicine, 2011; 110427140043047 DOI: 10.1056/NEJMoa1100066

Cite This Page:

McGill University. "Serendipity leads to lifesaving discovery: Team finds disease-causing mutations and saves a baby girl." ScienceDaily. ScienceDaily, 11 May 2011. <www.sciencedaily.com/releases/2011/05/110511101149.htm>.
McGill University. (2011, May 11). Serendipity leads to lifesaving discovery: Team finds disease-causing mutations and saves a baby girl. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2011/05/110511101149.htm
McGill University. "Serendipity leads to lifesaving discovery: Team finds disease-causing mutations and saves a baby girl." ScienceDaily. www.sciencedaily.com/releases/2011/05/110511101149.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) — An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins