Pediatric Pneumology, Immunology and Critical Care Medicine and SPZ (Center for Chronically Sick Children), Charité University Medicine Berlin, Berlin, Germany.
Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute (DRFZ), Berlin, Germany.
Lupus. 2020 Dec;29(14):1914-1925. doi: 10.1177/0961203320965699. Epub 2020 Oct 20.
To analyse the validity of membrane-bound SIGLEC1 (CD169) as a sensitive biomarker for monitoring disease activity in pediatric systemic lupus erythematosus (SLE).
27 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™ PE tubes. Associations between biomarkers and the clinical course were investigated by regression analysis.
In 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 (Δ) in SIGLEC1 levels during the clinical course is the only biomarker that significantly correlates with the change in SLEDAI-2k (beta = 0.28, p = 0.001). At follow-up visit, a clinically important worsening was experienced by 47.6% of patients with a Δ SIGLEC1 > 2 151 molecules/cell (OR 5.31) and 72.4% with a Δ SIGLEC1 > 756 molecules/cell (OR 8.90). Conversely, 36.4% of patients with a Δ SIGLEC1 < -2 818 molecules/cell (OR 4.16, percentiles as cut-off criteria) and 50.0% of patients with a Δ 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).
SIGLEC1 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.
分析膜结合型 SIGLEC1（CD169）作为监测儿童系统性红斑狼疮（SLE）疾病活动的敏感生物标志物的有效性。
对 27 名儿童和青少年 SLE 患者进行了平均 13.5 个月的随访。在连续的常规就诊中，测定了 SLEDAI-2k、C3、C4 和 ds-DNA 值。此外，通过流式细胞术测定单核细胞上的 SIGLEC1 表达。使用 QuantiBRITE™PE 管分析每个单核细胞结合的 PE 标记的 CD169 mAb 的量。通过回归分析研究生物标志物与临床过程之间的相关性。
一般来说，SLE 来源的单核细胞上的 SIGLEC1 表达水平较高（平均 6359（SD6056）个分子/单核细胞，截定点 2500 个分子/单核细胞），所有新诊断为 SLE 的患者均表现出升高的表达（平均 13366（SD7750）个分子/单核细胞）。在临床病程中 SIGLEC1 水平的变化（Δ）是唯一与 SLEDAI-2k 变化显著相关的生物标志物（β=0.28，p=0.001）。在随访时，47.6%的患者出现临床重要恶化，ΔSIGLEC1>2151 个细胞（OR5.31），72.4%的患者ΔSIGLEC1>756 个细胞（OR8.90）。相反，36.4%的患者ΔSIGLEC1<-2818 个细胞（OR4.16，采用百分位数作为截定点标准）和 50.0%的患者ΔSIGLEC1<-1370 个细胞（OR3.55，应用 Youden 指数）表现出临床改善。SIGLEC1 表达与治疗应用羟氯喹的量呈负相关（p<0.001）。
单核细胞上的 SIGLEC1 表达是儿童 SLE 疾病活动调整的敏感生物标志物，代表了一种有前途且易于应用的疾病监测工具。
