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Objective: Patients with systemic vasculitis (SV) have an increased risk of all-cause mortality, often due to infection, compared to the healthy population. We investigated whether humoral response to vaccination and biomarkers of immune dysfunction were associated with infection and death., Methods: Patients with SV in remission were vaccinated with pneumococcal 7-valent conjugate, Haemophilus influenzae type b, and meningococcal group C conjugate vaccine and meningococcal polysaccharide groups A, C, Y, and W135 vaccines. Total IgG and antibody titers against specific antigens and lymphocyte subset analysis were performed before vaccination. Postvaccination antibody titers were measured at 4 weeks and 2 years, from which an antibody response score was calculated. Infections and death following vaccination were collected prospectively following vaccination., Results: A total of 92 patients were safely vaccinated with no increase in disease relapse, median followup 4.6 years (interquartile range [IQR] 3.6-4.8 years). Eighteen patients died at a median of 2 years and the overall infection rate was 0.4 (IQR 0.2-1.3) infections/patient/year. Reduced serum IgG, B cell count, and CD4+ cell counts predicted poor vaccine response and infection but not death. The response rates to individual vaccine antigens was highly variable, with a median response rate of 46% (IQR 39-58%) of patients responding to each individual antigen. Vaccine response, age, and reduced renal function were independent predictors of all-cause mortality in multivariate analysis., Conclusion: Total IgG and B cell counts predict infection and response to vaccination. Vaccination in patients with SV in remission is safe and the response predicts all-cause mortality. Vaccine response is a surrogate marker of immune system health., (© 2016, American College of Rheumatology.)