The Researcher’s Summary:
Juvenile idiopathic arthritis (JIA) is the most common rheumatological disorder found in children, affecting one in 1,000. JIA leads to significant disability, and there is no known cause or cure. One hypothesis for how adult rheumatoid arthritis (RA) occurs is that infection and inflammation in the mouth, in the form of severe gingivitis, stimulates the immune system, which then goes on to react to the joints. Gingivitis is common, and who develops arthritis may be determined by the genes you are born with and how they react to oral infection.
Past work has determined that patients with RA are more likely to have gingivitis and antibodies that react to both proteins in the joints and oral bacteria. Little is known about the link between oral infection and arthritis in children. Moreover, JIA patients are very different from RA patients, in that they do not produce the same antibodies and they carry distinct genes.
Gingivitis occurs in up to 50 percent of children by the age of five years and peaks at almost 100 percent by puberty, decreasing again to 50 percent in adults. Thus, a treatable risk factor may be an important cause of JIA. We propose that a localized gene-specific immune response to P. gingivalis or other oral pathogens leads to a systemic inflammatory response with subsequent arthritis in children with JIA high-risk genes. We have shown that some of the inflammation-related proteins that are known to be high in infections are also high in JIA patients. We have also identified gene sequences in proteins important in fighting infections that are increased in frequency in JIA patients.
In the proposed project, we combine the expertise of a dentist-immunologist with a rheumatologist-immunologist and a clinical rheumatologist with expertise in assessing JIA patients for research. We will first test for increased frequency of severe gingivitis in children with JIA. Then we will test for a correlation between proinflammatory molecules in children with severe gingivitis vs. JIA. Finally, we will restore normal immune function in JIA cells by manipulating infection-related protein activity.
The results of this study will determine if there is a link between oral health and arthritis in children, and could lead to future studies in which we test for the power of oral hygiene to control infection, and to help treat JIA. In the public health realm, prevention of oral disease may not only be key adjuvant therapy for JIA, but also preventative in healthy children who are genetically predisposed to JIA.