An Emerging Role for Neutrophil Extracellular Traps in IgA Vasculitis: A Mini-Review

Chen, Xiuqi; Tu, Li; Tang, Qing; Huang, Lie; Qin, Yuan-Han

doi:10.3389/fimmu.2022.912929

Cited by 7 publications

(6 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Blockade of the LPS-LBP interaction was a strategy to limit neutrophil in ltration in a mouse sepsis model (22). As positive correlation was observed between LBP and blood neutrophil count, and LBP was higher in patients with neutrophil in ltrates compared to those with mixed immune cells in ltrates, inhibition of LBP-TLR4 pathway might represent a potential therapeutic option also in IgAV (23).…”

Section: Discussionmentioning

confidence: 99%

Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers

Bajželj,

Hladnik,

Blagus

et al. 2023

Preprint

View full text Add to dashboard Cite

Introduction Immunoglobulin A vasculitis (IgAV) in adults has a variable disease course, with patients often developing gastrointestinal and renal involvement and thus contributing to higher mortality. Due to understudied molecular mechanisms in IgAV currently used biomarkers for IgAV visceral involvement are largely lacking. Our aim was to search for potential serum biomarkers based on the skin transcriptomic signature. Methods RNA sequencing analysis was conducted on skin biopsies collected from 6 treatment-naïve patients (3 skin only and 3 renal involvement) and 3 healthy controls (HC) to get insight into deregulated processes at the transcriptomic level. 15 analytes were selected and measured based on the transcriptome analysis (adiponectin, lipopolysaccharide binding protein (LBP), matrix metalloproteinase-1 (MMP1), C-C motif chemokine ligand (CCL) 19, kallikrein-5, CCL3, leptin, C-X-C motif chemokine ligand (CXCL) 5, osteopontin, interleukin (IL)-15, CXCL10, angiopoietin-like 4 (ANGPTL4), SERPIN A12/vaspin, IL-18 and fatty acid-binding protein 4 (FABP4)) in sera of 59 IgAV and 22 HC. Machine learning was used to assess the ability of the analytes to predict IgAV and its organ involvement. Results Based on the gene expression levels in the skin, we were able to differentiate between IgAV patients and HC using principal component analysis (PCA) and a sample-to-sample distance matrix. Differential expression analysis revealed 49 differentially expressed genes (DEGs) in all IgAV patient’s vs HC. Patients with renal involvement had more DEGs than patients with skin involvement only (507 vs 46 DEGs) as compared to HC, suggesting different skin signatures. Major dysregulated processes in patients with renal involvement were lipid metabolism, acute inflammatory response, and extracellular matrix (ECM)-related processes. 11 of 15 analytes selected based on affected processes in IgAV skin (osteopontin, LBP, ANGPTL4, IL-15, FABP4, CCL19, kallikrein-5, CCL3, leptin, IL-18 and MMP1) were significantly higher (p-adj < 0.05) in IgAV serum as compared to HC. Prediction models utilizing measured analytes showed high potential for predicting adult IgAV. Conclusion Skin transcriptomic data revealed deregulations in lipid metabolism and acute inflammatory response, reflected also in serum analyte measurements. LBP, among others, could serve as a potential biomarker of renal complications, while adiponectin and CXCL10 could indicate gastrointestinal involvement.

show abstract

Section: Discussionmentioning

confidence: 99%

Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers

Bajželj,

Hladnik,

Blagus

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Nevertheless, a quick, reliable, and clinically meaningful identification method for circulating NETs has not been developed. In addition to the use of immunohistochemistry for the direct visualization of NETs, studies also report using surrogate markers such as cell-free DNA, MPO-DNA complexes, citrullinated histones C3, neutrophil elastase, and cathelicidin antimicrobial peptides [ 13 , 14 , 15 , 16 ]. Additionally, the presence of serologic NET markers has been correlated to increased SFL signals on Sysmex WDF scattergrams in patients with both acute and chronic inflammatory states [ 18 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, visual identification of NETs relies on the visualization of DNA, histones, myeloperoxidase, and neutrophil elastase, using advanced immunohistochemical staining and microscopic techniques [ 5 , 9 , 11 , 12 ]. Alternatively, cell-free DNA, MPO-DNA complexes, citrullinated histones C3, neutrophil elastase, and cathelicidin antimicrobial peptides are used as surrogate markers for NETosis [ 13 , 14 , 15 , 16 , 17 , 18 ]. Neutrophil activation marker CD66b has been described as positively correlating with side-fluorescent scatter (SFL) generated by the Sysmex system [ 18 , 19 ], with several reports suggesting that NETs are identified with Sysmex’ SFL scatters [ 18 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Identifying Neutrophil Extracellular Traps (NETs) in Blood Samples Using Peripheral Smear Autoanalyzers

Fedorov

Barouqa

Yin

et al. 2023

Life

View full text Add to dashboard Cite

Neutrophil Extracellular Traps (NETs) are large neutrophil-derived structures composed of decondensed chromatin, cytosolic, and granule proteins. NETs play an important role in fighting infection, inflammation, thrombosis, and tumor progression processes, yet their fast and reliable identification has been challenging. Smudge cells (SCs) are a subcategory of white cells identified by CellaVision®, a hematology autoanalyzer routinely used in clinical practice that uses digital imaging to generate “manual” differentials of peripheral blood smears. We hypothesize that a proportion of cells identified in the SC category by CellaVision® Hematology Autoanalyzers are actually NETs. We demonstrate that NET-like SCs are not present in normal blood samples, nor are they an artifact of smear preparation. NET-like SCs stain positive for neutrophil markers such as myeloperoxidase, leukocyte alkaline phosphatase, and neutrophil elastase. On flow cytometry, cells from samples with high percent NET-like SCs that are positive for surface DNA are also positive for CD45, myeloperoxidase and markers of neutrophil activation and CD66b. Samples with NET-like SCs have a strong side fluorescent (SFL) signal on the white count and nucleated red cells (WNR) scattergram, representing cells with high nucleic acid content. When compared to patients with low percent SCs, those with a high percentage of SCs have a significantly higher incidence of documented bacterial and viral infections. The current methodology of NET identification is time-consuming, complicated, and cumbersome. In this study, we present data supporting identification of NETs by CellaVision®, allowing for easy, fast, cost-effective, and high throughput identification of NETs that is available in real time and may serve as a positive marker for a bacterial or viral infections.

show abstract

“…73 FcαRI (CD89) has been shown to be lower in the urine of children with active IgAV, suggesting that the deposits remain in the kidneys and are not excreted. 74,75 In skin biopsies of patients with IC-SVV such as IgAV, NETs were present in the early stages of the disease and were significantly more abundant than in patients with urticarial vasculitis. 76 Their abundance was also correlated with the production of ROS.…”

Section: Ic Vasculitis: a Misdirected Activation Of The Prototypic An...mentioning

confidence: 99%

The neutrophil: A key resourceful agent in immune‐mediated vasculitis

Aymonnier

Amsler

Lamprecht

et al. 2022

Immunological Reviews

View full text Add to dashboard Cite

Neutrophils are no longer considered to be a highly differentiated and uniform population whose functions are solely confined to antimicrobial activities. This former restricted view of neutrophils as fixed effectors and that lack of plasticity was partly due to their characteristic short lifespan in circulation and very low transcriptional activity. 1-3 However, there has been increasing appreciation of the plasticity of neutrophils with the ongoing categorization of their subsets, including myeloid-derived suppressor cells and lowdensity neutrophils. Newly recognized neutrophil functions include the ability to communicate and modulate with almost all immune

show abstract

An Emerging Role for Neutrophil Extracellular Traps in IgA Vasculitis: A Mini-Review

Cited by 7 publications

References 68 publications

Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers

Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers

Identifying Neutrophil Extracellular Traps (NETs) in Blood Samples Using Peripheral Smear Autoanalyzers

The neutrophil: A key resourceful agent in immune‐mediated vasculitis

Contact Info

Product

Resources

About