Genetic Patterns Found in Children with CVID

A genome-wide association study (GWAS) searched for both common and rare genetic variants that would allow physicians to identify genetic patterns found in children with common variable immunodeficiency disease (CVID) but not in healthy children.

Using highly automated genotyping equipment at Children's Hospital's Center for Applied Genomics (Philadelphia, PA, USA), the study team performed a GWAS in a sample of 363 patients with CVID, compared to 3,031 healthy controls. The team 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 team also found SNPs in an area that codes for a family of proteins involved in immune responses.

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. The investigators are now working to refine the algorithm into a standardized diagnostic test for CVID. If the disorder could be diagnosed early, children may receive life-saving treatments before the disease can progress.

"These findings provide insight into the pathogenesis of CVID and its various subtypes, and may lead to future treatments," said Jordan S. Orange, MD, PhD, a pediatric immunologist at The Children's Hospital of Philadelphia (Pennsylvania, PA, USA) and co-lead author of the study.

"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 Dr. Orange. "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."

Dr. 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, the first genome-wide population-based study of CVID, appeared online April 15, 2011, in the Journal of Allergy and Clinical Immunology.

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