SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome

Abstract

ObjectivesTo evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-γ-inducible protein-10 (IP-10) in patients with primary Sjögren's syndrome (pSS).Methods31 patients fulfilling the American-European criteria for pSS were included. Disease activity was obtained by EULAR Sjögren's syndrome disease activity index (ESSDAI). SIGLEC1 expression on monocytes was analysed using flow cytometry. IP-10 concentrations were determined using Bioplex human Cytokine 27-plex kit. Spearman rank test (SRT) was used for correlation analysis and Mann-Whitney U (MWU) to test for differences between glandular and extraglandular manifestations.ResultsAn activated IFN system was detected by an upregulation of SIGLEC1 expression in 64.5% and by elevated serum level of IP-10 in 78.9% of our patients with pSS. In a subsequent analysis SIGLEC1 expression was found to be upregulated more frequently in patients with extraglandular manifestations (16/16, 100%) compared to patients with exclusively glandular involvement (4/15, 27%). SIGLEC1 expression could significantly discriminate between these two disease subgroups (p=0.0001, MWU) with a positive predictive value (PPV) of 80% for extraglandular disease. Moreover, the expression correlated with disease activity (p=0.005, r=0.54, SRT). Serum IP-10 levels neither differed significantly between glandular and extraglandular disease nor correlated with ESSDAI.ConclusionsOur results indicate that increased SIGLEC1 expression characterises patients with systemic involvement and high disease activity. Therefore, SIGLEC1 determination might be of value for subset definition, risk stratification and differential therapeutic considerations in pSS.

The Diagnosis and Treatment of Sjögren’s Syndrome

“…Siglec-1 has recently emerged as a new biomarker. This indirect interferon marker correlates with a high level of disease activity as well as extraglandular manifestations (27).…”

Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome

“…Thus, sPD-1 constitutes an interesting area for additional research. CXCL9 and CXCL10 are chemokines of the C-X-C chemokine family, which have both been reported to be upregulated at the mRNA and protein level in various tissues of patients with pSS 35–38. In fact, CXCL10 has previously been proposed as a surrogate marker for IFN activity in patients with SLE 39 40.…”

Interferons and innate immune activation in autoimmune congenital heart block

“…SIGLEC-1, also called sialoadhesin or CD169, is one of the most upregulated cell surface-expressed genes in the IFN signature of patients with SLE or SS and correlates with disease activity. [54][55][56][57] Of note, the same study found that the levels of IP-10 (CXCL10), a protein induced by both type I and type II IFNs and also correlating with disease activity in SLE, 55 did not differ between CHB mothers and mothers of unaffected children. 53 Since this initial study, activation of the type I IFN system and increased expression of SIGLEC-1 have been reported both in cord blood mononuclear cells (CBMCs) from neonates of anti-Ro/La antibody-positive mothers 58 and in heart tissues from foetuses dying with autoimmune CHB.…”

“…In addition, levels of SIGLEC‐1, a protein expressed on myeloid cells and induced by type I IFN, were also significantly higher in autoimmune CHB mothers. SIGLEC‐1, also called sialoadhesin or CD169, is one of the most upregulated cell surface‐expressed genes in the IFN signature of patients with SLE or SS and correlates with disease activity 54‐57 . Of note, the same study found that the levels of IP‐10 (CXCL10), a protein induced by both type I and type II IFNs and also correlating with disease activity in SLE, 55 did not differ between CHB mothers and mothers of unaffected children 53 .…”