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The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus

Title: The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus
Authors: Oliveira, JJ
Karrar, S
Rainbow, DB
Pinder, CL
Clarke, P
Garcia, AR
Al-Assar, O
Burling, K
Morris, S
Stratton, R
Vyse, TJ
Wicker, LS
Todd, JA
Ferreira, RC
Item Type: Journal Article
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.
Issue Date: 27-Jul-2018
Date of Acceptance: 20-Jun-2018
URI: http://hdl.handle.net/10044/1/67880
DOI: https://dx.doi.org/10.1186/s13075-018-1649-1
ISSN: 1478-6354
Publisher: BMC
Journal / Book Title: Arthritis Research and Therapy
Volume: 20
Issue: 1
Copyright Statement: © 2018 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Soluble SIGLEC-1
Type I interferon
1103 Clinical Sciences
1107 Immunology
1117 Public Health And Health Services
Arthritis & Rheumatology
Publication Status: Published
Article Number: 152
Online Publication Date: 2018-07-27
Appears in Collections:Department of Medicine (up to 2019)