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Arthritis Rheum. 2008 Apr;58(4):1136-45. doi: 10.1002/art.23404.

Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus.

Author information

1
Charité Universitätsmedizin Berlin, Humboldt University of Berlin, Germany.

Abstract

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.

PMID:
18383365
DOI:
10.1002/art.23404
[Indexed for MEDLINE]
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