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Best of 2012

Nailing Difficult Diagnoses

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Best of Nailing Difficult Diagnosis header

Our Immunology Diagnostic Laboratory develops tests – and makes difficult diagnoses – that help children with immune disorders lead longer, healthier lives.  

 

Seattle Children’s Immunology Diagnostic Laboratory (IDL) is known throughout the world for its ability to quickly and accurately make diagnoses that other labs can’t.

In 2012, the IDL made progress toward innovative new tests that screen children for severe combined immunodeficiency disorder (SCID) and for mutations in more than 200 genes that are linked to immune disorders. The lab also helped illuminate how the gene FOXP3 controls T cells that regulate the immune system.

The IDL’s testing and research helps physicians around the world identify the best way to treat children suffering from immune disorders and lays the foundation for therapies that could counteract everything from autoimmune diseases to cancer.

“We’re giving patients answers that we couldn’t give them just a few years ago,” says Dr. Troy Torgerson, the lab’s co-director. “And that’s helping them lead longer, healthier lives.”

Helping doctors diagnose rare diseases

The IDL is developing a testing panel that quickly sequences 200 genes now known to cause immunodeficiency. Researchers across the globe identify new immunodeficiency-related gene mutations every few weeks; this test will help the lab identify whether a patient has one of the newly discovered mutations. The IDL will use the test to diagnose more than 150 immune disorders, such as agammaglobulinemia and Wiskott-Aldrich syndrome.

“Right now, we routinely sequence about 40 genes, so this new panel will increase that number substantially,” says Torgerson. “This lets us give doctors a more comprehensive answer about which disorder their patient has so they can select the best treatment.”

New test for severe combined immunodeficiency disorder

Best of 2012 Nailing Difficult Diagnosis Header

Torgerson is also working with the Washington State Department of Health to add a test to the standard screenings all newborns receive that would detect SCID, a rare disease that can make it impossible for the immune system to fight infections. SCID is fatal unless treated by bone marrow transplant or gene therapy. The IDL is developing a testing panel that would evaluate the babies identified by newborn screening for mutations in the 21 genes known to cause SCID.

“That would help us catch SCID early, when we have a really good chance of curing it with a bone marrow transplant,” Torgerson says.

Taking the brakes off the immune system

The lab also helps Torgerson unravel how a mutation in the gene FOXP3 causes immune dysregulation polyendocrinopathy enteropathy X-linked syndrome, or IPEX. When male babies are born with IPEX, their immune systems attack their bodies, triggering diabetes, inflammatory bowel disease and other serious health problems. Most affected children die before age 2.

FOXP3 controls the development and function of regulatory T cells – cells that control how aggressively other immune cells ramp up their activity to fight infections and then tell them to calm down when the threat has passed. Patients with IPEX do not have functional regulatory T cells. Torgerson and his colleagues are studying ways to give those cells new instructions.

“If we can figure out how to improve regulatory T cell activity, we can treat IPEX and possibly other autoimmune diseases,” says Torgerson. “On the other hand, if we can temporarily turn down regulatory T cell activity, it would be like taking the brakes off the immune system, so it could rev up and attack cancer.”

Better outcomes for children with IPEX

In studying patients with IPEX, Torgerson’s team determined that regulatory T cells rapidly multiply after bone marrow transplant, so only a small proportion of cells from the bone marrow donor are needed to correct the disease. This led the researchers to realize they could lower the intensity of bone marrow transplants for children with IPEX. Dr. Lauri Burroughs and Torgerson are leading a clinical trial that could make this lower-intensity regimen standard practice for patients with IPEX.

“Instead of wiping out a patient’s entire immune system, we can leave much of it in place and rely on the donated regulatory T cells to integrate and help it recover,” he says.

A personal quest to improve patients’ lives

The IDL’s progress validates Torgerson’s quest to conduct research that improves everyday treatment. He eagerly shares stories of patients his team has helped, including a young man who recently went to college to study social work.

“It’s pretty awesome to think about how, because we saved his life with a bone marrow transplant, he’s going on to help others,” Torgerson says. “We want all of our patients to have that success – that’s why we keep hammering away.”

Seattle Children’s Immunology Diagnostic Lab is developing a testing panel that quickly sequences 200 genes now known to cause immunodeficiency. The current panel routinely sequences about 40.