Featured Research

from universities, journals, and other organizations

For puzzling childhood immune disorder, gene research opens door to first diagnostic test

Date:
May 11, 2011
Source:
Children's Hospital of Philadelphia
Summary:
A new genomics study sets the stage for the first predictive diagnostic test in a serious immunodeficiency disease in children. If the disorder, common variable immunodeficiency disease (CVID), can be diagnosed early, children may receive life-saving treatments before the disease can progress.

A new genomics study, led by the Center for Applied Genomics at The Children's Hospital of Philadelphia, sets the stage for the first predictive diagnostic test in a serious immunodeficiency disease in children. If the disorder, common variable immunodeficiency disease (CVID), can be diagnosed early, children may receive life-saving treatments before the disease can progress.

Related Articles


"Currently, there may be a delay of up to nine years from the first time a child becomes sick from this very complex disease until he or she is diagnosed," said Jordan S. Orange, M.D., Ph.D., a pediatric immunologist at The Children's Hospital of Philadelphia and co-lead author of the study. "During this delay, a child may suffer repeated infections and life-shortening organ damage. Identifying CVID at an early stage may allow physicians to intervene earlier with appropriate treatment."

At Children's Hospital, Orange directs the Jeffrey Modell Diagnostic Center and cares for children with primary immunodeficiency diseases. Orange collaborated with Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia, Charlotte Cunningham Rundles, M.D., of Mt. Sinai School of Medicine, New York City, and researchers from several other institutions.

The research, the first genome-wide population-based study of CVID, appeared online April 15 in the Journal of Allergy and Clinical Immunology.

In CVID, a child has a low level of antibodies (specifically immunoglobulins), reducing the body's ability to fight disease, and leaving the child vulnerable to recurrent infections. CVID can first occur early or later in life, and the symptoms are highly variable. Frequent respiratory infections may lead to permanent lung damage. Patients may also suffer joint inflammation, stomach and bowel disorders, and a higher risk of cancers.

The great variability of the disease, coupled with the lack of a clear-cut diagnostic test, often causes CVID to go undiagnosed for years before doctors can initiate treatment. The complexity of the disease has also frustrated attempts to identify causes.

In the current study, the research team conducted a genome-wide association study (GWAS) to search for both common and rare genetic variants that might allow physicians to identify genetic patterns found in children with CVID but not in healthy children.

Using highly automated genotyping equipment at Children's Hospital's Center for Applied Genomics, the study team performed a GWAS in a sample of 363 patients with CVID, compared to 3,031 healthy controls. They searched for single-nucleotide polymorphisms (SNPs) as well as for rarer copy number variations (CNVs). SNPs are changes in a single base of DNA, while CNVs are deleted or repeated sequences in a stretch of DNA.

The GWAS detected a strong association with genes in the major histocompatibility complex (MHC) region, an area known to play an important role in immune-related conditions, and previously linked to CVID. The researchers also found SNPs in an area that codes for a family of proteins involved in immune responses.

In its CNV research the study team also found more than a dozen novel genes with direct or potential relevance to the immune system. The gene discoveries provided clues to the largely unknown biology of how CVID develops, shedding light on the biological mechanisms underlying the disease. "These findings provide insight into the pathogenesis of CVID and its various subtypes, and may lead to future treatments," said Orange.

The GWAS findings confirmed the genetic complexity of CVID, but more importantly for clinical application, the researchers were able to use their discoveries to develop a predictive algorithm. When they tested that algorithm on cohorts of CVID cases and controls, they were able to distinguish CVID from healthy controls with 99 percent accuracy.

The investigators are now working to refine the algorithm into a standardized diagnostic test for CVID. Orange added, "This is very exciting. It suggests that we may be able to use a patient's genetic profile at an early stage to predict whether he or she will develop CVID. Since earlier treatment may greatly improve a child's ability to live with CVID, this research may represent an important advance in managing a complex, puzzling disease."

The study was funded by an Institutional Development Award to the Center for Applied Genomics from The Children's Hospital of Philadelphia. Other funding sources came from the National Institutes of Health, the Jeffrey Modell Foundation, the Cotswold Foundation and NIHR Oxford Biomedical Research Center.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jordan S. Orange, Joseph T. Glessner, Elena Resnick, Kathleen E. Sullivan, Mary Lucas, Berne Ferry, Cecilia E. Kim, Cuiping Hou, Fengxiang Wang, Rosetta Chiavacci, Subra Kugathasan, John W. Sleasman, Robert Baldassano, Elena E. Perez, Helen Chapel, Charlotte Cunningham-Rundles, Hakon Hakonarson. Genome-wide association identifies diverse causes of common variable immunodeficiency. Journal of Allergy and Clinical Immunology, 2011; DOI: 10.1016/j.jaci.2011.02.039

Cite This Page:

Children's Hospital of Philadelphia. "For puzzling childhood immune disorder, gene research opens door to first diagnostic test." ScienceDaily. ScienceDaily, 11 May 2011. <www.sciencedaily.com/releases/2011/05/110511142140.htm>.
Children's Hospital of Philadelphia. (2011, May 11). For puzzling childhood immune disorder, gene research opens door to first diagnostic test. ScienceDaily. Retrieved November 25, 2014 from www.sciencedaily.com/releases/2011/05/110511142140.htm
Children's Hospital of Philadelphia. "For puzzling childhood immune disorder, gene research opens door to first diagnostic test." ScienceDaily. www.sciencedaily.com/releases/2011/05/110511142140.htm (accessed November 25, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, November 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
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