Sjogren's syndrome is a common autoimmune disease characterized by focal lymphocytic infiltration of exocrine glands. Although Sjogren's syndrome is associated with significant morbidity, the etiology is unknown, and diagnosis is difficult. To date, the most useful biomarker for Sjogren's syndrome is the presence of anti-Ro and anti-La autoantibodies. These antibodies are directed against ribonucleoprotein particles (RNPs) consisting of the Ro60 protein, the La protein, and nocoding RNAs called Y RNAs. However, while antibodies to Ro60 and/or La occur in 38-90% of Sjogren's syndrome patients, these antibodies also occur in patients with other rheumatic diseases, including systemic lupus erythematosus. The objective of this exploratory project is to identify novel biomarkers that will expedite correct diagnosis of Sjogren's syndrome and yield insights into etiology and/or disease progression. Our specific approach is to focus on newly identified components of the Ro60 RNPs and on oxidatively modified forms of Ro60. Our first aim is to determine whether any of nine novel Ro-associated proteins are specific targets of the immune response in Sjogren's syndrome. Our second aim is to examine the tissue distribution and subcellular localization of these proteins. The finding that a targeted protein is most abundant in salivary epithelial cells, while other proteins are more abundant in keratinocytes, may give insights into why some patients with anti-Ro60 antibodies develop Sjogren's syndrome, while others develop distinct rheumatic diseases. Our third aim is to determine if anti-Ro60 autoantibodies are preferentially directed against oxidatively modified forms of the protein. The finding that patients target oxidized forms of Ro60 may be helpful for differentiating the various syndromes associated with these antibodies, may be useful for predicting clinical outcomes, and may yield insights into the mechanisms by which autoimmunity in Sjogren's syndrome originates. [unreadable] [unreadable] Lay summary: Sjogren's syndrome, a disease characterized by dry eyes and dry mouth, is often confused with other illnesses. Our goal is to identify whether Sjogren's syndrome patients produce autoantibodies that will be useful for diagnosis and for predicting the course of the disease in individual patients. [unreadable] [unreadable] [unreadable]