Siglec1 (Cd169) Is A Sensitive Biomarker For The Deterioration Of The Clinical Course In Childhood Systemic Lupus Erythematosus

BackgroundTo analyse the validity of membrane-bound SIGLEC1 (CD169) as a sensitive biomarker for monitoring disease activity in pediatric systemic lupus erythematosus (SLE).Methods27 children and adolescents with SLE were followed for a mean of 13.5 months. During consecutive routine visits SLEDAI-2k, C3, C4 and ds-DNA values were determined. Additionally, expression of SIGLEC1 on monocytes was determined by flow cytometry. The amount of PE-labelled CD169 mAb bound per monocyte was analyzed using QuantiBRITE (TM) PE tubes. Associations between biomarkers and the clinical course were investigated by regression analysis.ResultsIn general, SIGLEC1 expression is high on SLE-derived monocytes (mean 6 359 (SD 6 056) molecules/monocyte, cut-off 2 500 molecules/monocyte), all patients with newly diagnosed SLE exhibit elevated expression (mean 13366 (SD 7 750) molecules/monocyte). Changes (Delta) in SIGLEC1 levels during the clinical course is the only biomarker that significantly correlates with the change in SLEDAI-2k (beta(ST) = 0.28, p = 0.001). At follow-up visit, a clinically important worsening was experienced by 47.6% of patients with a Delta SIGLEC1 > 2 151 molecules/cell (OR 5.31) and 72.4% with a Delta SIGLEC1 > 756 molecules/cell (OR 8.90). Conversely, 36.4% of patients with a Delta SIGLEC1 < -2 818 molecules/cell (OR 4.16, percentiles as cut-off criteria) and 50.0% of patients with a Delta SIGLEC1 < -1 370 molecules/cell (OR 3.55, application of Youden index) showed clinical improvement. SIGLEC1 expression correlates inversely with the amount of therapeutically applied hydroxychloroquine (p < 0.001).ConclusionsSIGLEC1 expression on monocytes is a sensitive biomarker for adjusting disease activity in childhood SLE and represents a promising and easily applicable tool for disease monitoring.