PS1:11 The interferon biomarker siglec1 reflects disease activity in paediatric systemic lupus erythematosus. (21st March 2018)

• Record Type: Journal Article
• Authors: Sae Lim, VS; Klotsche, J; Heinrich, M; Thumfart, J; Biesen, R; Meisel, C; Unterwalder, N; Kallinich, T
• Is Part Of: Lupus science & medicine. Volume 5(2018)Supplement 1
• Page Start: A37
• Page End: A38
• Publication Date: 2018-03-21
• Subjects: Paediatric SLE -- biomarker -- disease activity; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2018-abstract.60
• Languages: English
• ISSNs: 2398-8851

Abstract

Abstract : 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<0.012), but not with the C3 (108 determinations, betaST 0.03, p=0, 80), the C4 (106 determinations, betaST −0.06, p<0.58) and the anti-dsDNA-antibodies (104 determinations, betaST 0.06, p=0.61). SIGLEC1 is a more change-sensitive biomarker than the conventional laboratory parameters C3, C4 and ds-DNA-Ab.Patients with an increase in SIGLEC1 of >1120 molecules/monocyte between two visits show a higher probability (OR=7.0, p<0.001) of minimal clinical worsening (SLEDAI more/equal 2 points). Patients who show a decrease >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.