Our research aims to understand the molecular mechanisms responsible for disease risk and severity in juvenile idiopathic arthritis (JIA). Through basic-science and translational research, we hope to identify the genetic components of JIA, provide a molecular basis for diagnosing the disease and use biomarkers to predict responses to treatments.
We have focused on defining the basis for genetic risk for JIA and, through gene expression profiling, identifying distinct molecular profiles related to the various subtypes of JIA. In 2009, we completed JIA genomic datasets of unprecedented scope, including high-resolution HLA allele types, single nucleotide polymorphisms (SNP) and copy number variant genotypes for about 1,000 patients and 1,000 controls, as well as gene expression profiles for a subset of about 200 patients. Results from each of our datasets suggest that patients who develop rheumatic disease at a young age share a common biological basis that is different from patients who develop the disease later in life.
Our genetic association studies revealed risk factors unique to JIA and its subtypes, but also revealed a set of risk factors common to both JIA and other autoimmune diseases, such as lupus and Crohn’s disease. Our studies defined human leukocyte antigen (HLA) associations with greater precision than previously possible. And, gene expression studies using blood samples obtained from patients at the onset of JIA have revealed an increased presence and function of various immature cell types including B-cells, monocytes and macrophages.
Together, these genomic studies provide evidence for a fundamental shift toward molecular definitions for JIA. Our findings may lead to a re-evaluation of the present clinical criteria for defining JIA’s subtypes, and could provide insight into the disease’s origins and pathogenesis.