Activation of the interferon‐α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease

作者：Kyriakos A. Kirou, Christina Lee, Sandhya George, Kyriakos Louca, Margaret G. E. Peterson, Mary K. Crow · 发表于：Arthritis & Rheumatism · 年份：2005 · DOI：10.1002/art.21031 · 被引用次数：708 · 研究领域：Systemic Lupus Erythematosus Research、interferon and immune responses、Rheumatoid Arthritis Research and Therapies

OBJECTIVE: Gene-expression studies have demonstrated increased expression of interferon (IFN)-inducible genes (IFIGs) in peripheral blood mononuclear cells (PBMCs) of many patients with systemic lupus erythematosus (SLE), with a predominant effect of type I IFN. This study examined the hypothesis that increased disease severity and activity, as well as distinct autoantibody specificities, characterize SLE patients with activation of the type I IFN pathway. METHODS: Freshly isolated PBMCs from 77 SLE patients, 22 disease controls, and 28 healthy donors were subjected to real-time polymerase chain reaction for 3 IFIGs that are preferentially induced by IFNalpha, and the data were used to derive IFNalpha scores for all individuals. Expression of IFIGs was significantly higher in SLE patients compared with disease controls or healthy donors. SLE patients with high and low IFNalpha scores were compared for clinical manifestations of disease, disease severity, disease activity, serologic features, and potential confounders, by bivariate and multivariate analyses. RESULTS: SLE patients with a high IFNalpha score had a significantly higher prevalence of renal disease, a greater number of American College of Rheumatology criteria for SLE, and a higher Systemic Lupus International Collaborating Clinics damage index (SDI) score than did SLE patients with low IFNalpha scores. Patients with high scores showed increased disease activity, as measured by lower C3 levels, hemoglobin levels, a...