The goal of this study is to understand intrinsic and extrinsic defects in influenza vaccination responses in systemic lupus erythematosus (SLE) patients. SLE is a prototypic autoimmune disease characterized by high titers of autoantibodies. We enrolled 72 patients to evaluate anti-influenza antibody responses, autoantibody titers and disease activity after vaccination. In addition, detailed clinical and demographic information was collected. Individuals received the current influenza vaccine and sera were collected at baseline, 2, 6, and 12 weeks post vaccination. Based upon post-vaccination antibody responses, relative antibody affinities and hemaglutination inhibition levels, patients were grouped into "high" and "low" responders. Surprisingly, the high responder group was enriched in older subjects and African Americans. Patients with high anti-influenza antibodies had an increased frequency of discoid rash and anti-nRNP autoantibodies, while patients with low antibody responses had an increase in hematological criteria and anti-aPL autoantibodies. Interestingly, several patients had increased autoantibody titers following vaccination, but there were no significant associated increases in disease flare. In summary, specific demographic, clinical, and autoantibody features were associated with poor antibody responses to influenza vaccination in SLE patients. NIH: NO1-AI-50026