Objective. Type I interferon (IFN) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE) and is therefore considered a potential therapeutic target. This study was undertaken to establish a feasible biomarker for IFN effects with respect to disease activity and effectiveness of IFN-suppressive therapy in SLE patients. Methods. Transcriptomes of purified monocytes from 9 SLE patients and 7 healthy controls were analyzed by Affymetrix GeneChip technology. Levels of sialic acid-binding Ig-like lectin 1 (Siglec-1) (sialoadhesin, CD169) in inflammatory and resident monocytes were determined at the protein level in 38 healthy controls and 52 SLE patients, using multicolor flow cytometry. Results. Transcriptomes of peripheral monocytes from SLE patients revealed a dominant type I IFN signature. Siglec-1 was identified as one of the most prominent type I IFN-regulated candidate genes. At the protein level, the frequency of Siglec-1-expressing monocyte subsets was correlated with disease activity (as measured by the SLE Disease Activity Index) and was inversely correlated with levels of complement factors. Most interestingly, levels of anti-double-stranded DNA (anti-dsDNA) antibodies were highly correlated with the percentage of resident monocytes, but not inflammatory monocytes, expressing Siglec-1. High-dose glucocorticoid treatment resulted in a dramatic reduction of Siglec-1 expression in cells from patients with active SLE. Conclusion. Our findings indicate that Siglec-1 expression in resident blood monocytes is a potential biomarker for monitoring disease activity, displaying type I IFN responses, and estimating levels of anti-dsDNA antibodies. Moreover, our results suggest that resident and inflammatory monocytes contribute differently to the process of autoantibody formation in SLE.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)