VirScan Profiling in Pediatric Rheumatic Diseases
Principle Investigator: Susan Thompson, PhD
Juvenile idiopathic arthritis (JIA) encompasses a range of clinical subtypes each with a complex genetic architecture and unknown environmental influences. The most common form of disease presents at less than 6 years of age with fewer than five joints and is termed oligoarticular JIA. These early-onset oligoarticular JIA patients are often positive for antinuclear antibodies and at risk for chronic anterior uveitis, a type of eye inflammation with no equivalent disease in adults. It has long been suspected that this form of JIA represents a reaction to viral infection, since it tends to occur after a child no longer has their mother’s immunity and during a time of frequent upper respiratory and gastrointestinal illness. Unfortunately, the sheer number of human viruses make this hypothesis difficult to test.
A new methodology, termed VirScan, can be used for screening of blood samples for antibodies specific for over 200 viruses, making it possible to assemble the full past infectious history of a donor from a banked sample of serum or plasma. Accordingly, we have successfully implemented this technology in our laboratory and evaluated about 100 early onset JIA patient samples and 100 matched control samples as part of a pilot study funded by the Arthritis Foundation and CARRA, a North American Childhood Arthritis research alliance. This pilot data, although not definitive to report certain viral etiology in early onset JIA, found sufficient specificity and sensitivity and has identified several candidates for replication and validation studies.
We will extend the pilot experiments to two additional rheumatic diseases affecting children to compare with early-onset seronegative JIA and to potentially provide new clues to their etiology. Kawasaki disease and systemic JIA samples are available and provide extraordinary opportunities to generate new hypotheses. Systemic JIA (sJIA) is rare and characterized by systemic inflammation distinguishable from other forms of JIA by clinical features and treatment responses that are like autoinflammatory diseases. Kawasaki disease (KD) is an acute febrile illness of early childhood characterized by vasculitis and sometimes coronary artery aneurysms. KD occurs during specific seasons of the year and tends to affect children of Asian descent. These features are consistent with genetic contributions to the illness.
We expect that patients will exhibit over-representation of particular viruses, families of antigenically related viruses, or number of past infections. We expect different findings between diseases that inform about disease pathophysiology and potentially lead to disease prevention. In addition, we will extend the expertise we develop to Cincinnati Children’s investigators studying diseases such as lupus, multiple sclerosis, juvenile dermatomyositis and type 1 diabetes.