Uncovering New Clues About Juvenile Rheumatoid Arthritis
Why will one child develop juvenile rheumatoid arthritis (JRA) and not others, even within the same family? And once diagnosed with JRA, why do some children respond well to common medications – and others don't?
Scientists now believe that as many as eight to 12 genes from among the 20,000 to 40,000 we each possess are responsible, genes from both sides of the family. David Glass, MD, director of the Division of Rheumatology, emphasizes that JRA is characterized as a complex genetic trait. "Probably a dozen different single nucleotide polymorphisms, the elements that generate variation within any given gene, are responsible for this disease," he says. "It's vital to identify them and the combinations that together may cause JRA and predict its outcome or response to treatment." In addition to those combinations of genes generating the risk for JRA, others are able to prevent the onset of the disease.
Pediatric rheumatologists at Cincinnati Children's, recognized internationally for their work in JRA and other immunological diseases, continue to make great progress in identifying the genetic causes of JRA. Their studies have identified genes and several chromosome regions as potential contributors to either JRA susceptibility or resistance.
Today the Human Genome Project and major advances in computational technology offer researchers at Cincinnati Children's unrivaled opportunities to unlock the genetic basis of JRA. "We can now simultaneously evaluate all 20,000 to 40,000 genes in the genome. Looking for genes used to be a fishing expedition, but not any more, thanks to the comprehensive, systematic exploration of the whole genome available to us," explains Dr. Glass.
Because Cincinnati Children's already houses a JRA research registry of more than 600 families known to have a genetic susceptibility to JRA, as well as the national JRA Affected Sib Pair Registry, rheumatology researchers have ready access to DNA for analysis. They are applying advanced genotyping and tracking systems to identify the genes and their expression patterns, a process known as integrative genomics. Researchers hope these gene expression patterns will establish new markers of disease that may provide a molecular basis for treatment decisions at early stages of JRA.
A team of researchers, recruiters and laboratory experts collaborate to increase understanding of the biological pathways and processes that underlie JRA. They are: Sandy Kramer; Lori Luyrink; Marta Moraldo, MD; William Nichols, PhD; Kim Phelan; Mimi Ryan; Edie Shear; Shweta Srivastava; Marc Sudman; Susan Thompson, PhD; and Monica Tsoras. Research funding comes from Fifth Third Bank, National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Ohio River Valley Chapter of the Arthritis Foundation, and the Cincinnati Children's Research Foundation.
