Mayo researchers lead team that discovers role of dendritic cells in childhood autoimmune disease
Significance of the Research
Provides new strategy for designing better treatments
Mayo Clinic researchers, working with colleagues at the University of Minnesota and University of Pittsburgh, are the first to describe a new role for a specialized cell of the immune system in children suffering from a rare muscle-damaging disease known as juvenile dermatomyositis (JDM). The specialized cells, called dendritic cells, have never before been found inside muscle tissue of JDM patients -- a discovery that suggests they are tightly linked to initiation of the disease process. The finding opens new possibilities for designing better treatments for JDM, and possibly for other related diseases such as multiple sclerosis, rheumatoid arthritis and lupus.
The Mayo Clinic-led research team report will be presented Nov. 14 as part of the American College of Rheumatology’s annual meeting in San Diego, Calif., held Nov. 12-17.
Mayo Clinic researchers compared samples of muscle tissue from children with JDM to children with other disorders. Their findings are important not only for determining what causes JDM and designing new treatments for it, but for understanding an entire class of diseases in which the body’s immune system gets mixed up and attacks "self" as if it were a foreigner, or "nonself." These are known as autoimmune diseases, and there are about 80 distinct autoimmune disorders. As a group, they are relatively common and include rheumatoid arthritis, lupus and multiple sclerosis. Autoimmune disorders share the general trait of the body failing to recognize itself, and erroneously mounting an immune attack that destroys function. Insights gained in JDM may possibly be applied to other autoimmune diseases.
Explains Ann Reed, M.D., Mayo Clinic pediatric rheumatologist/immunologist who led the investigation: "Under the microscope, it looked so dramatic to see the dendritic cells maturing in the muscle tissue and then migrating out into the bloodstream -- and to realize it was a process which no one has ever documented before. And it was a surprise. Usually few dendritic cells reside in muscle as immature cells; they sort of hang out in case they’re needed in an immune response. But, we determined that they are actually maturing in the muscle tissues in response to something in the muscle tissue itself."
This finding is important because a central question in JDM research has always been: Do the dendritic cells get activated in muscle tissue? Or, do they get activated outside of the tissue? The research by Mayo Clinic and collaborators provides the first proof that the dendritic cells get activated inside muscle tissues and then may move out into the bloodstream. Says Dr. Reed: "When you think about it as a clinician, it’s really exciting because it shows what is happening in the muscle that starts the disease -- and holds out the possibility that it is maybe something that we can turn off in new treatments we develop by targeting the mechanism in the muscle tissue. And that’s really neat stuff for our patients."
JDM is a rare (5 in 1 million children) autoimmune disorder of young children characterized by inflammation of the blood vessels under the muscle and skin. This results in muscle damage, as well as in tissue changes of skin over the eyelids, finger joints and knuckles. Symptoms appear gradually and include: muscle pain and tenderness; difficulty swallowing, which results in weight loss; irritability; fatigue; fever; and rash around the eyelids, finger joints, knuckles, elbows, ankles or knees.
Diagnosis may involve the following: blood tests to detect muscle enzymes and markers of inflammation; an electromyography (EMG) to assess nerve or muscle damage; muscle biopsy for examination; X-rays; and MRI. While there is no cure for JDM, there are treatment options. They include medications to reduce inflammation and skin rashes; physical and occupational therapy to improve muscle function; and nutritional support. Children with JDM may suffer organ failure in the same way transplant patients often do when their bodies fail to accept donated organs in graft-versus-host disease.
Lisa Lucier | EurekAlert!
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