Network analysis of associations between serum interferon-alpha activity, autoantibodies, and clinical features in systemic lupus erythematosus.

摘要

OBJECTIVE: Interferon-alpha (IFNalpha) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFNalpha levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. This study was undertaken to detect associations between clinical and serologic disease manifestations and serum IFNalpha activity in a large diverse SLE cohort, using multivariate and network analyses. METHODS: We studied 1,089 SLE patients (387 African American, 186 Hispanic American, and 516 European American patients). The presence or absence of individual American College of Rheumatology (ACR) clinical criteria for SLE, autoantibodies, and serum IFNalpha activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each ancestral background group separately to establish the network of associations between variables that were independently significant following Bonferroni correction. RESULTS: In all ancestral backgrounds, high IFNalpha activity was associated with anti-Ro and anti-double-stranded DNA antibodies (P = 4.6 x 10(-18) and P = 2.9 x 10(-16) , respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFNalpha activity (P 1 ancestral background. Associations between clinical criteria were different for different ancestral backgrounds, while autoantibody-IFNalpha relationships were similar across backgrounds. IFNalpha activity and autoantibodies were not associated with ACR clinical features in multivariate models. CONCLUSION: Our findings indicate that serum IFNalpha activity is strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFNalpha may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations.