Researchers at Seattle's Children's Hospital Uncover Clues to Solving a Long-Standing Medical Puzzle

A new study by researchers at Children’s Hospital and Regional Medical Center and the University of Washington (UW) provides a better understanding of the rare, inherited disorder of the immune system called Wiskott-Aldrich Syndrome (WAS).

A new study by researchers at Children’s Hospital and Regional Medical Center and the University of Washington (UW) provides a better understanding of the rare, inherited disorder of the immune system called Wiskott-Aldrich Syndrome (WAS).

WAS is an inherited disorder of the immune system that affects males, and becomes symptomatic in early childhood. It is characterized by recurrent infections, bleeding due to low platelet numbers, and eczema (a chronic skin rash).

The disorder is caused by a mutation in the Wiskott-Aldrich Syndrome protein (WASp) gene. At this time, bone marrow transplant is the only known cure.

While most studies have focused on understanding the defects in T cell activation caused by the WASp deficiency, researchers at Children’s Hospital and the UW in Seattle have now found that in mice and humans a population of T cells known as regulatory T cells, which keep other immune cells from attacking the body’s own tissues and causing autoimmunity, are also impaired in the absence of WASp.

“By studying one of our patients as well as animals, we found that WASp is needed to keep regulatory T cells alive. This helps to explain why, despite their immune deficiency, that so many WAS patients have severe autoimmune problems,” said Dr. David Rawlings, lead researcher and section head of Immunology at Children’s Hospital and the UW.

“It is another rewarding example of where our patients’ willingness to assist in our research has lead to a fundamental insight into the human immune system.”

In the Jan. 11 issue of the Journal of Clinical Investigation, Dr. David Rawlings and colleagues uncovered a role for regulatory T cells in what was previously viewed as a paradox: WAS patients experienced both immune-deficiency (inability to fight off infections) as well as autoimmunity (inappropriate immune responses against their own cells and tissues).

These researchers have been working to develop a cure for WAS by replacing the deficient gene in the patient’s bone marrow using gene therapy. Based on this study and others these gene corrected cells (including the regulatory T cells) have a growth advantage, meaning that they can outcompete and thereby eventually outnumber the deficient cells.

These findings provide important new information regarding signals that keep regulatory T cells alive. It suggests that gene therapy for WAS will not only restore the ability to fight off infections but should also block autoimmunity. These observations may also lead to strategies to harness regulatory T cells to combat other autoimmune disorders such as diabetes, arthritis, and lupus.

In addition to Dr. David Rawlings, other authors of the study are Stephanie Humblet-Baron, Immunology, Stephanie Anover, research supervisor, Immunology, Shirley Becker-Herman, Socheath Khim, research scientist, Immunology, Thuc Nguyen, Hans Ochs, MD, chief, Immunology Clinic at Children’s Hospital, and Troy Torgerson, MD, Rheumatology at Children’s Hospital.

A complete copy of the study is available at the Journal of Clinical Investigation website.

About Seattle Children’s

Seattle Children’s Hospital, Foundation and Research Institute together deliver superior patient care, advance new discoveries and treatments through pediatric research, and raise funds to create better futures for patients. Consistently ranked as one of the top 10 children’s hospitals in the country by U.S. News & World Report, Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental needs of children from infancy through young adulthood. Through the collaboration of physicians in nearly 60 pediatric subspecialties, Seattle Children’s Hospital provides inpatient, outpatient, diagnostic, surgical, rehabilitative, behavioral, and emergency and outreach services to families from around the world.

Located in downtown Seattle’s biotech corridor, Seattle Children’s Research Institute is pushing the boundaries of medical research to find cures for pediatric diseases and improve outcomes for children all over the world. Internationally recognized investigators and staff at the research institute are advancing new discoveries in cancer, genetics, immunology, pathology, infectious disease, injury prevention, bioethics and much more.

Seattle Children’s Hospital and Research Foundation and Seattle Children’s Hospital Guild Association work together to gather community support and raise funds for uncompensated care, clinical care and research. The foundation receives nearly 80,000 gifts each year, from lemonade stand proceeds to corporate sponsorships. Seattle Children’s Hospital Guild Association is the largest all-volunteer fundraising network for any hospital in the country, serving as the umbrella organization for 450 groups of people who turn an activity they love into a fundraiser. Support from the foundation and guild association makes it possible for Seattle Children’s care and research teams to improve the health and well-being of all kids.

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