The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

João J. Oliveira, Sarah Karrar, Daniel B. Rainbow, Christopher L. Pinder, Pamela Clarke, Arcadio Rubio García, Osama Al-Assar, Keith Burling, Sian Morris, Richard Stratton, Tim J. Vyse, Linda S. Wicker, John A. Todd, Ricardo C. Ferreira

ABSTRACT

BACKGROUND: The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). METHODS: We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504). Samples from systemic sclerosis patients (n = 99) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n = 656). RESULTS: Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score. CONCLUSIONS: Our sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte-macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in clinical trials. More... »

PAGES

152

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-018-1649-1

DOI

http://dx.doi.org/10.1186/s13075-018-1649-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105878066

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30053827


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    "description": "BACKGROUND: The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1).\nMETHODS: We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n\u2009=\u200975) and healthy donors (n\u2009=\u2009504). Samples from systemic sclerosis patients (n\u2009=\u200999) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n\u2009=\u2009656).\nRESULTS: Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score.\nCONCLUSIONS: Our sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte-macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in\u00a0clinical trials.", 
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278 https://www.grid.ac/institutes/grid.83440.3b schema:alternateName University College London
279 schema:name UCL Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital Campus, Rowland Hill Street, London, UK
280 rdf:type schema:Organization
 




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