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[0] Thompson, Linda [1] Responses to Influenza Vaccination in Systemic Lupus [2] Oklahoma Medical Research Foundation (OMRF) [3] NO1-AI-50026* [4] 
The goal of the proposed work is to understand why many patients with systemic lupus erythematosus (SLE) fail to make adequate responses to immunization with the influenza vaccine. Our approach is to compare the major components of the normal immune response to vaccination in SLE patients and control subjects in order to identify abnormalities in this group of immunocompromised individuals. These are the first steps in devising a strategy to modify the current vaccine protocol to improve the immune response of SLE patients and other individuals undergoing immunosuppressive therapy. Objective I. To establish and serially follow a collection of SLE patients and matched controls before and after influenza vaccination (or documented influenza infection). Objective II. To evaluate the antibody responses of SLE patients and controls to influenza vaccination to determine the relative titers and specificities of protective vs. non-protective antibodies. Objective III. To analyze the differentiation of influenza-specific B cells in SLE patients and controls following immunization and to generate and characterize anti-influenza monoclonal antibodies. Objective IV. To evaluate the expression levels of regulatory molecules of B cell signaling by flow cytometry and to determine whether signaling thresholds are altered in SLE patients compared to controls. Objective V. To evaluate T cell responses to influenza vaccination by measuring IFN production and CD4 T cell activation. Objective VI. To evaluate changes in autoantibody titers, specificities and epitopes in SLE patients who are high and low responders to immunization with the influenza vaccine. The results of the above studies will reveal which step(s) in the normal response to influenza immunization are defective in SLE patients. Characteristics of SLE patients who will not make an adequate response to immunization will also be identified. These are the first steps in devising a strategy to modify the current vaccine protocol in order to improve the immune response of SLE patients and other individuals undergoing immunosuppressive therapy.
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