Association of Endogenous Anti-Interferon-alpha Autoantibodies With Decreased Interferon-Pathway and Disease Activity in Patients With Systemic Lupus Erythematosus

作者：Morimoto Alyssa M^*; Flesher Donna Thibault; Yang Jihong; Wolslegel Kristen; Wang Xiangdan; Brady Ann; Abbas Alexander R; Quarmby Valerie; Wakshull Eric; Richardson Bruce; Townsend Michael J; Behrens Timothy W

来源：Arthritis and Rheumatism, 2011, 63(8): 2407-2415.

DOI：10.1002/art.30399

Objective. Numerous observations implicate interferon-alpha (IFN alpha) in the pathophysiology of systemic lupus erythematosus (SLE); however, the potential impact of endogenous anti-IFN alpha autoantibodies (AIAAs) on IFN-pathway and disease activity is unclear. The aim of this study was to characterize IFN-pathway activity and the serologic and clinical profiles of AIAA-positive patients with SLE.
Methods. Sera obtained from patients with SLE (n = 49), patients with rheumatoid arthritis (n = 25), and healthy control subjects (n = 25) were examined for the presence of AIAAs, using a biosensor immunoassay. Serum type I IFN bioactivity and the ability of AIAA-positive sera to neutralize IFN alpha activity were determined using U937 cells. Levels of IFN-regulated gene expression in peripheral blood were determined by microarray, and serum levels of BAFF, IFN-inducible chemokines, and other autoantibodies were measured using immunoassays.
Results. AIAAs were detected in 27% of the serum samples from patients with SLE, using a biosensor immunoassay. Unsupervised hierarchical clustering analysis identified 2 subgroups of patients, IFN(low) and IFN(high), that differed in the levels of serum type I IFN bioactivity, IFN-regulated gene expression, BAFF, antiribosomal P, and anti-chromatin autoantibodies, and in AIAA status. The majority of AIAA-positive patients had significantly lower levels of serum type I IFN bioactivity, reduced downstream IFN-pathway activity, and lower disease activity compared with the IFN(high) patients. AIAA-positive sera were able to effectively neutralize type I IFN activity in vitro.
Conclusion. Patients with SLE commonly harbor AIAAs. AIAA-positive patients have lower levels of serum type I IFN bioactivity and evidence for reduced downstream IFN-pathway and disease activity. AIAAs may influence the clinical course in SLE by blunting the effects produced by IFN alpha.

• 出版日期2011-8