Gene Research Opens Door to First Diagnostic Test for Common Variable Immunodeficiency

Featured In: Academia News | Genomics

Thursday, May 12, 2024

Get daily Bioscience Technology industry top stories and headlines - Sign up now!

newsvine diigo google
slashdot
Share
Loading...

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.

Earlier diagnosis and treatment of condition needed
“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, MD, PhD, 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, MD, PhD, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia, Charlotte Cunningham Rundles, MD, 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 in the Journal of Allergy and Clinical Immunology.

About common variable immunodeficiency
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.

Genome study identifies gene mutations associated with CVID
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.

Researchers develop predictive algorithm to predict CVID
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.”

Source: Children's Hospital of Philadelphia

Join the Discussion
Rate Article: Average 0 out of 5
register or log in to comment on this article!

0 Comments

Add Comment

Text Only 2000 character limit

Page 1 of 1

Research Exchange

Bringing the Cell Image into Focus

Nov 2 2010

Improvements in transmission electron microscope (TEM) technology increase the power of this imaging tool for the study of cell biology.

Finding a Cure for Spinal Cord Injury with On-Demand LIMS

Oct 25 2010

The Miami Project to Cure Paralysis finds an on-demand laboratory information management system (LIMS) helps to accelerate discovery in its HCS projects.

Saving Cells: Image Processing for Improved Viability, Part II: Iterative Deconvolution

Oct 25 2010

3D light microscopy and deconvolution provide a means to investigate 3D structure, providing near-confocal quality images without the temporal requirements or potentially damaging phototoxicity associated with other 3D imaging technologies. This article is Part II in a series regarding viability, resolution improvement, and measurement in fluorescence imaging. Part I focused on spectral unmixing.

Saving Cells: Image Processing for Improved Viability

Sep 22 2010

This article is Part I of a two-part series regarding viability, resolution improvement, and measurement in fluorescence imaging. Part II will focus on deconvolution.

Evaluation of a New Nano-Type UV-Vis Spectrophotometer

Mar 3

Analysis of one- to four-microliter size samples for nucleic acids has become routine in many life science laboratories. However, until now, available instruments require considerable manipulation of the instrument and sample; some require manually recording the data. The user must typically lower and raise the arm manually, then wipe the sample manually from the target after each analysis. And fiberoptics used in some of these instruments are subject to deterioration.

Production of Recombinant Proteins and Monoclonal Antibodies in Hollow Fiber Bioreactors

Jan 25

While well-understood, robust and convenient, classical batch-style 2-D culture on non-porous supports or 3-D suspension culture in other devices are really not very biologically relevant models. Cell culture conditions can affect the quality of the antibody or protein produced.

Selecting Robots for Use in Drug Discovery and Testing

Dec 6 2010

Drug discovery and testing, with their need for speed, repeatability and verification, are ideally suited to benefit from robot automation. It is therefore not surprising that robots have been at the forefront of automation developments in both these areas.

HP Scalable Network Storage Systems for Life Sciences

Sep 13 2010

Life sciences research today is advancing exponentially, each step bringing us closer to the realization of truly personalized medicine–preventive care and treatments designed specifically for each individual. In the near future, PCPGM healthcare researchers expect to be able to use predictive genetic testing to create custom treatment plans for individuals and deliver dramatic improvements over today’s one-size-fits-all approach. But research capabilities are only part of the equation; current storage and operating capacities must also evolve to accommodate ever-expanding amounts of data before the goal of personalized medicine can be realized.

Using the Tecan Genesis Workstation to Automate a Cytometric Bead Array (CBA) Immunoassay

Mar 11 2010

The poster describe the process involved in automating a Cytometric Bead Array (CBA) immunoassay developed to measure relative concentrations of serum antibodies against Tetanus (TT), Sperm Whale Myoglobin (SWM) and Keyhole Limpet Hemocyanin (KLH) in KLH-immunized volunteers.

Ensuring Quality in Assays Performed with Automated Liquid Handlers

Feb 2 2010

The focus of this presentation is to highlight the need of ensuring quality in important assays performed with automated liquid handlers. Nearly all assays performed within a laboratory are volume-dependent. In turn, all concentrations of biological and chemical components in these assays, as well as the associated dilution protocols, are volume-dependent. Because analyte concentration is volume-dependent, an assay’s results might be falsely interpreted if liquid handler variability and inaccuracies are unknown or if the system(s) go unchecked for a long period.

Inkjet System for Protein Crystallography

Feb 1 2010

X-ray crystallography is used routinely by scientists to obtain the three dimensional structure of a biological molecule of interest.Such information can be used to determine how a pharmaceutical interacts with a protein target and what changes might improve functionality. However, the crystallization of macromolecules still remains a serious hindrance in structural determination despite impressive advances in screening methods and technologies.

Attention Deficit & Hyperactivity in a Drosophila Memory Mutant

Attention Deficit & Hyperactivity in a Drosophila Memory Mutant

Nov 9 2009

Action selection is modulated by external stimuli either directly or via memory retrieval. In a constantly changing environment, animals have evolved attention-like processes to effectively filter the incoming sensory stream. These attention-like processes, in turn, are modulated by memory. The neurobiological nature of how attention, action selection and memory are inter-connected is unknown. We describe here new phenotypes of the memory mutant radish in the fruit fly Drosophila.

Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET

3 hours ago

PURPOSE: (18)F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull...

Analyses of phenotypic and functional characteristics of CX3CR1-expressing natural killer cells

11 hours ago

Summary We previously demonstrated a correlation between the frequency of CX3CR1-expressing human natural killer (NK) cells and disease activity in multiple sclerosis and showed that CX3CR1(high) NK cells were more cytotoxic than their CX3CR1(neg/low)...

Identification and characterization of a bioactive lantibiotic produced by Staphylococcus warneri (82)

12 hours ago

Bacillus thuringiensis is widely used as agricultural biopesticide for a long time. As a producing strain, B. thuringiensis subsp. chinensis strain CT-43 has high toxin to lepidopterous and dipterous insects. It can form various parasporal crystals consisting of...

Identification and characterization of a bioactive lantibiotic produced by Staphylococcus warneri (81)

13 hours ago

Bacillus thuringiensis is widely used as agricultural biopesticide for a long time. As a producing strain, B. thuringiensis subsp. chinensis strain CT-43 has high toxin to lepidopterous and dipterous insects. It can form various parasporal crystals consisting of...

Prokariotic Cell Collection in Denmark

Nov 6 2009

I would like to know about a prokariotic cell collection in Denmark. Is there a cell bank in this country? I need a Lactobacillus strain for a fermentation assay and this information about the bank is very helpful for me.

Request for Entries

Oct 16 2009

Ask the Experts is your chance to get the answers to questions on applications, materials, methods, processes, and technologies. Email you question to bst_web@advantagemedia.com, and the editors of Bioscience Technology will find an appropriate expert to answer it. Watch this space in the future to see the questions your colleagues are posting.

STAY INFORMED: SUBSCRIBE TO

Magazine and E-mail Newsletters

Loading...
E-mail:   

MULTIMEDIA

Video:

Viewing SureFocus Slides

Jun 11 2010

A demonstration of SureFocus Microscope Slides in the review of AFB Smears. SureFocus Slides are a patent-pending breakthrough in tuberculosis detection, as their fluorescent staining circle remains visible during review, Fluorescence Microscopy.

Podcasts:

Allen Institute for Brain Research

Allen Institute for Brain Research

Oct 14 2009

Discussed in this interview are both the mouse brain project and the human cortex project with an emphasis on the importance of these projects to neuroscience research.

Top Stories and Headlines
EVERYDAY!

FREE Email Newsletter

Information: