CVID genetic testing

[Guest guest]

I apologize in advance if someone has already posted this study.

http://www.eurekalert.org/pub_releases/2011-05/chop-fpc051111.php

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

diagnostic test

Study at the Children's Hospital of Philadelphia yields causes of common

variable immunodeficiency

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.

" 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 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. "

[Guest guest]

does anyone have access to this study?

Thanks,

________________________________

From: kristinz4 <kristin-smith@...>

Sent: Thu, May 19, 2011 5:31:13 PM

Subject: CVID genetic testing

 

I apologize in advance if someone has already posted this study.

http://www.eurekalert.org/pub_releases/2011-05/chop-fpc051111.php

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

diagnostic test

Study at the Children's Hospital of Philadelphia yields causes of common

variable immunodeficiency

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.

" 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 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. "