Dataset Information

SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus.

ABSTRACT:

Background

To analyse the validity of membrane-bound SIGLEC1 (CD169) as a sensitive biomarker for monitoring disease activity in pediatric systemic lupus erythematosus (SLE).

Methods

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.

Results

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_ST = 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).

Conclusions

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.

SUBMITTER: Stuckrad SLV

PROVIDER: S-EPMC7684796 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus.

Stuckrad Sae Lim von SLV Klotsche Jens J Biesen Robert R Lieber Mareike M Thumfart Julia J Meisel Christian C Unterwalder Nadine N Kallinich Tilmann T

Lupus 20201020 14

<h4>Background</h4>To analyse the validity of membrane-bound SIGLEC1 (CD169) as a sensitive biomarker for monitoring disease activity in pediatric systemic lupus erythematosus (SLE).<h4>Methods</h4>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 ...[more]

PMID: 33081587

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Project description:BackgroundIFN-induced protein 44-like (IFI44L) promoter methylation has been demonstrated to serve as an effective blood diagnostic biomarker for adult-onset SLE. However, its utility as a diagnostic marker for childhood-onset SLE (cSLE) remains to be verified.MethodsInitially, we conducted a differential analysis of gene methylation and mRNA expression patterns in cSLE whole blood samples obtained from the public GEO database to determine IFI44L gene expression and assess the methylation status at its CpG sites. Subsequently, we collected clinical whole blood samples from 49 cSLE patients and 12 healthy children, employing an HRM-qPCR-based IFI44L methylation detection technique to evaluate its diagnostic efficacy in pediatric clinical practice.ResultsA total of 26 hypomethylated, highly expressed genes in cSLE were identified by intersecting differentially expressed genes (DEGs) and differentially methylation genes (DMGs). GO enrichment analysis for these 26 genes indicated a robust association with type I IFN. Among the overlapping genes, IFI44L exhibited the most pronounced differential expression and methylation. In subsequent clinical validation experiments, IFI44L methylation was confirmed as an effective blood-based diagnostic biomarker for cSLE, achieving an AUC of 0.867, a sensitivity of 0.753, and a specificity of 1.000.ConclusionsIFI44L methylation is a promising blood biomarker for cSLE.ImpactIFI44L promoter methylation was reported to serve as a highly sensitive and specific diagnostic marker for adult-onset SLE. However, the diagnostic efficacy of IFI44L in childhood-onset SLE (cSLE) still remains to be confirmed. In this study, we utilized bioinformatics analysis and conducted clinical experiments to demonstrate that IFI44L methylation can also serve as a promising blood biomarker for cSLE. The findings of this study can facilitate the diagnosis of cSLE and broaden our understanding of its molecular mechanisms, with a particular focus on those related to type I interferons.

Project description:Background: Accumulating evidence suggests that differentially expressed non-coding circular RNAs (circRNAs) play critical roles in the progress of autoimmune diseases. However, the role of circRNAs in systemic lupus erythematosus (SLE) remains unclear. Methods: We initially used next-generation sequencing (NGS) to comprehensively analyze circRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from 10 SLE patients, stratified by their disease activity characteristics (stable or active SLE), and 10 healthy controls (HCs). Candidate circRNAs identified were first validated by quantitative reverse-transcription (qRT)-PCR in PBMC samples from a training-phase cohort of five SLE patients and five HCs. The significantly dysregulated circRNAs were then confirmed by qRT-PCR in a validation cohort of 23 SLE patients and 21 HCs, and in an external validation cohort with 64 SLE patients, 58 HCs, and 50 patients with rheumatoid arthritis (RA). In addition, we conducted bioinformatics analysis and western blotting investigating the relationships between the candidate circRNAs and SLE progression. Results: Multilayer integrative analysis of circRNA regulation showed that 84 circRNAs were upregulated and 30 were downregulated in patients with SLE compared with HCs. We then analyzed the intersection of these differentially expressed circRNAs in an SLE-stable cohort, an SLE-active cohort, and HCs. This enabled us to narrow down dysregulated circRNAs to 15 upregulated circRNAs. Only hsa_circ_0000479 was significantly upregulated in PBMCs of patients with SLE compared with HCs (P < 0.05). Furthermore, the diagnostic potential of hsa_circ_0000479 expression to distinguish SLE patients from HCs and RA patients was also significantly increased in the validation-phase and external-validation-phase cohorts (P < 0.05). When distinguishing SLE patients from HCs, the diagnostic specificities of hsa_circ_0000479 were 0.619 and 1.0 in two validation cohorts, respectively (AUCs = 0.731 and 0.730, respectively). It was also significantly increased in either stable SLE patients or active SLE patients compared with HCs in these two cohorts (P < 0.05). We also used bioinformatics analysis to show that hsa_circ_0000479 regulates SLE progression by modulating metabolic pathways and the Wnt signaling pathway. Western blotting revealed that the expression of Wnt-16 protein was significantly decreased in SLE. Conclusion: Our results suggest that hsa_circ_0000479 has potential as a novel biomarker for the diagnosis of SLE.

Dataset Information

SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus.

Background

Methods

Results

Conclusions

Publications

SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus.

Similar Datasets

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