Research Description

The Role of Antinuclear Antibodies in Autoimmunity

Autoimmune diseases are generally diagnosed when the immune system mis-identifies one or more of body’s organs as “non-self” and then mounts an attack on one or more organ systems, such as the connective tissues, endocrine system, nervous system, respiratory system, circulatory system or digestive system. Autoantibodies-- antibodies against the body’s own proteins-- often develop before the onset of an autoimmune disease. In particular, Antinuclear Antibodies (ANAs) are antibodies against the various antigens of the cell nucleus. These antibodies are sometimes the first indication that an autoimmune disease may develop. However, many ANA positive patients may never develop an autoimmune disease. The ultimate goal of this research project is to determine which patients with a positive ANA titer are more likely to develop an autoimmune disease.

In this study, 170 patients found to have a positive ANA test but no autoimmune disease in a previous study will be re-evaluated five years later for the development of an autoimmune disease. These patients will be contacted by phone and administered a questionnaire inquiring about specific symptoms of autoimmune diseases. If the development of an autoimmune disease is suspected—based on the questionnaire-- the patient will be requested to come to the University of Florida General Clinic Research Center, where a physical exam will be administered by a rheumatologist. Patients will be categorized into two groups. One category will consist of patients testing positive for ANAs who have developed an autoimmune disease (lupus, scleroderma, polymyositis, Sjogren’s syndrome, rheumatoid arthritis, or autoimmune thyroiditis) over the five or more years of observation. The other group will consist of individuals who have remained disease-free for at least five years after the positi ve ANA was discovered. The patients with clinical evidence of an autoimmune disease will have blood drawn. Individual autoantibodies will be identified using an immunoprecipitation assay. The expression of interferon inducible genes (a biomarker for lupus) will be measured by real- time PCR, and the number of antibody secreting cells will be quantified by flow cytometry. These studies will address two questions. The first is: What is the risk of developing an autoimmune disease in otherwise healthy individuals who are found to have a positive ANA test? Secondly: Are there specific types of autoantibodies, cytokines (e.g. interferon), or circulating blood cells that can be used to identify the individuals at highest risk for developing autoimmune disease?