Arthritis & Rheumatism, April 2008, Vol.58(4), pp.1136-1145
OBJECTIVEType 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. METHODSTranscriptomes 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. RESULTSTranscriptomes 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. CONCLUSIONOur 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.
Adult–Blood ; Aged–Blood ; Biomarkers–Metabolism ; Case-Control Studies–Immunology ; Female–Metabolism ; Gene Expression Profiling–Metabolism ; Humans–Metabolism ; Lupus Erythematosus, Systemic–Metabolism ; Male–Metabolism ; Membrane Glycoproteins–Metabolism ; Middle Aged–Metabolism ; Monocytes–Metabolism ; Receptors, Immunologic–Metabolism ; Severity of Illness Index–Metabolism ; Sialic Acid Binding Ig-Like Lectin 1–Metabolism ; Abridged ; Biomarkers ; Membrane Glycoproteins ; Receptors, Immunologic ; Siglec1 Protein, Human ; Sialic Acid Binding Ig-Like Lectin 1;