Oxidative T Cell Modifications in Lupus and Sjogren's Syndrome.

Abstract

OBJECTIVES: Lupus flares are triggered by environmental agents that cause oxidative stress, but the mechanisms involved are unclear. The flares are characterized by oxidative modifications of proteins by 4-hydroxynonenals, malondialdehydes, carbonyls and nitration. These modifications have been proposed to induce and perpetuate lupus flares by "altered self" mechanisms. An epigenetically altered CD4+CD28+ T cell subset, caused at least in part by nitration of T cell signaling molecules, is found in patients with active lupus, and nitrated T cells are sufficient to cause lupus-like autoimmunity in animal models. The relation of protein 4-hydroxynonenals, malondialdehydes, carbonyls and nitration to lupus flares though, is unknown. We tested if the size of the epigenetically altered subset is related to disease activity and one or more of these oxidative modifications in lupus patients. We also tested the relationship between subset size, disease activity and the same oxidative modifications in Sjogren's syndrome, another autoimmune disease also associated with oxidative stress and characterized by anti-nuclear antibodies and the presence of the subset. METHODS: Lupus flare severity was quantitated using the Systemic Lupus Erythematosus Disease Activity Index, and Sjogren's flare severity using the European Sjogren's Syndrome Disease Activity Index. Subset size was determined by flow cytometry. Protein modifications were determined by ELISA. RESULTS: Only protein nitration correlated with the size of the subset in lupus and Sjogren's syndrome. CONCLUSIONS: These results support a role for protein nitration in subset size and lupus flare severity. Protein nitration may also contribute to autoantibody formation in Sjogren's syndrome.