PS1:11 The interferon biomarker siglec1 reflects disease activity in paediatric systemic lupus erythematosus

Introduction SIGLEC1 (sialic acid-binding Ig-like lectin 1, CD169) is a monocytic adhesion molecule induced by interferon – α. In adult systemic lupus erythematosus (SLE), SIGLEC1 correlates cross-sectionally and longitudinally with disease activity. The aim of this work was to examine whether SIGLEC1 also reflects the disease activity in paediatric SLE. Methods Over a period of 29 months the disease activity was clinically evaluated using SLEDAI (SLE-Disease Activity Index-2000). In 28 consecutive paediatric SLE patients (mean age 16 years, range 3–38 years, 86% female, 14% male), the number of SIGLEC1 molecules per CD14 +on blood monocyte was quantified using flow cytometry. At the same time, the level of anti-ds DNA-antibody titer (ELISA) and the concentration of complement factors C3 and C4 (nephelometry) were determined. The association between SIGLEC1, C3, C4 and ds DNA-antibody with SLEDAI was estimated using a mixed linear model to model the repeated measurement of parameters within a patient. The cut-off for the change in SIGLEC1 between two consecutive visits to predict minimal clinical improvement or worsening in SLEDAI was chosen on the maximum Youden Index. Results The density of SIGLEC1 molecules on the surface of monocytes based on two visits, correlated with the SLEDAI (128 determinations, betaST 0.22, p 1120 molecules/monocyte between two visits show a higher probability (OR=7.0, p 2902 SIGLEC1 molecules/monocyte have a higher chance (OR=6.3, p=0.004) to have a clinical improvement (SLEDAI more/equal 2 points). Conclusion This prospective cohort study showed for the first time the significant relationship between the routinely measured interferon biomarker SIGLEC1 and the disease activity in paediatric SLE patients. Thus, SIGLEC1 represents a potential marker for activity monitoring in this disease.