The Stevens lab investigates the causes of autoimmune diseases, and pursues innovative new treatments for a variety of childhood disorders.
Learn more about the lab's projects and research areas:
Maternal microchimerism and autoimmune diseases
The Stevens lab is investigating whether maternal microchimerism - a phenomenon where cells are transferred from mother to fetus and remain in the child - could play a role in triggering autoimmune diseases.
Dr. Anne Stevens and her colleagues helped prove that a mother's cells stay in her child's blood and organs for years. Since these cells are foreign to the child, it would seem likely that the child's immune system would see the maternal cells as invaders and attack them. The Stevens team is unraveling how the body is programmed to tolerate maternal cells - and whether mistakes in that process trigger autoimmune diseases by causing the immune system to turn against maternal cells.
Investigating PDL1 in patients with lupus
In healthy people, a protein called PDL1 acts as an "off switch" on the surface of infection-fighting T cells. The protein keeps T cells under control by limiting their number and suppressing their activity. But this system can break down. The Stevens lab discovered that PDL1 is often missing on the cells of children with active lupus. This potentially explains why their immune system spins out of control and turns against them.
The Stevens lab is trying to pinpoint exactly how the body produces and regulates PDL1, and is investigating ways to fix this process when it malfunctions. For instance, enzymes called caspases can destroy PDL1, and these enzymes are overactive in children with lupus. Stevens and her colleagues are testing drugs that inhibit these enzymes, with hopes that the drugs could restore PDL1 in patients with lupus.
Helping doctors choose the right treatment for lupus patients
The Stevens lab developed a test that helps doctors choose the right treatment by determining if a child with lupus is having a lupus flare or is suffering from an infection. In the case of a lupus flare, the patient needs drugs that will suppress the immune system's attacks. If the child has an infection, doctors can decrease medications that suppress the immune system, helping it fend off the infection.
- Learn more about the test at Quest Diagnostics.
Studying a drug that could improve lupus treatment
The Stevens lab is partnering with Kineta Inc., a Seattle-based biotechnology company, on a collaboration called the Alliance for Children's Therapeutics (ACT). ACT investigates whether an innovative drug, ShK-186, could be an effective treatment for systemic lupus erythmatosus (SLE). The drug is designed to suppress immune activity by blocking a chemical pathway, called KV1.3, that activates certain immune cells and controls whether they proliferate.
The Stevens team is studying the role of KV1.3 channels in children with lupus kidney diseases (lupus nephritis, or LN). These studies are the foundation for future research on whether ShK-186, which potentially stops immune cells from attacking patients, can be an effective treatment for SLE and LN.
This lupus research could pave the way toward better treatments for several autoimmune diseases including multiple sclerosis, type I diabetes and rheumatoid arthritis.
- If you're interested in participating in a lupus research study, please email Dr. Anne Stevens. Children with lupus and healthy kids can participate and accelerate progress toward new treatments.
Understanding the genetics of lupus
Because lupus strikes children so early in life, it is probably caused by a child's genes more than by exposure to something in the environment, like a virus or a food. Stevens and her colleagues are investigating whether children with lupus have different genes than adults with the disease, and are trying to pinpoint which genes spark disruptions in the PDL1 pathway. This could set the stage for therapies that correct or suppress those genes, or their downstream effects.
- Email Dr. Anne Stevens to learn more about participating in a lupus genetics research study.
Developing treatment guidelines for pediatric scleroderma
Stevens is leading an innovative project to develop the first treatment guidelines for children with systemic scleroderma, a rare autoimmune condition that hardens the skin and causes internal scarring that can damage vital organs. Some doctors use high-dose chemotherapy and steroids to treat the condition, while others use bone marrow transplantation. But no research studies have examined whether these treatments are effective, and some doctors prefer to treat only the disease's symptoms without resorting to toxic therapies that could harm the patient.
Now Stevens is working with an alliance of pediatric rheumatologists across North America to build the infrastructure for multisite clinical trials to study which treatments are best for systemic sclerosis. She is collecting a pool of patients who can participate in the trials, and is part of a team that is developing a registry of more than 250 children with scleroderma - a vital resource that will accelerate the progress of researchers nationwide.
- Read a Seattle Children's article about how Stevens is improving scleroderma treatment with an approach that has led to remission in some patients.
Studying possible links between maternal microchimerism and scleroderma
The Stevens lab is studying a potential connection between scleroderma and maternal microchimerism - the presence of a mother's cells in her fetus and child. The lab is investigating whether there are proteins on these cells that stimulate the immune system and cause it to attack patients. If Stevens and her colleagues can identify these proteins and understand how they work, it could lead to treatments that let doctors block the proteins without using chemotherapy to suppress the immune system.
Investigating scleroderma's genetic causes
Adults can have genes that increase their chances of getting scleroderma. The Stevens lab is investigating whether pediatric scleroderma also has genetic roots. If there are genetic similarities between adult and pediatric scleroderma patients, it may be possible to treat children with the same techniques now used on adults.
- Email Dr. Anne Stevens to learn more about participating in a scleroderma research study.
Juvenile Idiopathic Arthritis
Can gingivitis lead to juvenile idiopathic arthritis?
Stevens and her colleagues are investigating whether gingivitis triggers juvenile idiopathic arthritis (JIA), which is the most common childhood rheumatological disorder. Researchers have made this connection in adult rheumatoid arthritis patients, where the antibodies that attack oral bacteria also contribute to arthritis by attacking proteins in the joints.
In children, Stevens suspects that the immune system's attempts to fend off gingivitis may escalate into inflammation that affects the joints and causes JIA. To study this link, the Stevens team is first investigating whether severe gingivitis is unusually common in children with severe JIA. If they confirm this connection, the researchers will try to identify which molecules contribute to JIA. They will also explore the possibility that simply improving children's oral health could reduce the chances that children who are predisposed to JIA will contract the disease. Stevens received the Arthritis Foundation's 2012 Clifford M. Clarke Science Award for this pioneering work.
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