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

Objectives: To evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-gamma-inducible protein-10 (IP-10) in patients with primary Sjogren's syndrome (pSS). Methods: 31 patients fulfilling the American-European criteria for pSS were included. Disease activity was obtained by EULAR Sjogren'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. Results: An 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. Conclusions: Our 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.