FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4317829683> ?p ?o ?g. }

• W4317829683 endingPage "648" @default.
• W4317829683 startingPage "636" @default.
• W4317829683 abstract "Abstract Background Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. Objectives We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324. Methods Biopsy and peripheral blood samples were taken from participants of two studies: 2018.206, a noninterventional research study of systemic and dermal neutrophils and inflammatory markers in patients with neutrophilic skin diseases, and CSL324_1001 (ACTRN12616000846426), a single-dose ascending and repeated dose, randomized, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy adult subjects. Ex vivo experiments were performed, including neutrophil enumeration and immunophenotyping, migration, receptor occupancy and transcriptome analysis. Results The number of cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) was significantly higher in HS lesions compared with biopsies from healthy donors (HDs) (P &lt; 0.0001 and P = 0.0223, respectively). In peripheral blood samples, mean neutrophil counts were significantly higher in patients with HS than in HDs (2.98 vs. 1.60 × 109 L–1, respectively; P = 8.8 × 10–4). Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher mean CXCR1 on the surface of neutrophils in patients with HS (24453.20 vs. 20798.47 for HD; P = 0.03). G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from patients with HS compared with HDs (mean 6.61 vs. 3.84 pg mL–1, respectively; P = 0.013). Administration of CSL324 inhibited G-CSF-induced transcriptional changes in HDs, similar to those observed in the HS cohort, as highlighted by expression changes in genes related to neutrophil migratory capacity. Conclusions Data suggest that neutrophils contribute to HS pathophysiology and that neutrophils are increased in lesions due to an increase in G-CSF-driven migration. CSL324 counteracted G-CSF-induced transcriptomic changes and blocked neutrophil migration by reducing cell-surface levels of chemokine receptors." @default.
• W4317829683 created "2023-01-24" @default.
• W4317829683 creator A5000222857 @default.
• W4317829683 creator A5003966117 @default.
• W4317829683 creator A5014102803 @default.
• W4317829683 creator A5014721642 @default.
• W4317829683 creator A5021107172 @default.
• W4317829683 creator A5028901693 @default.
• W4317829683 creator A5031203411 @default.
• W4317829683 creator A5035608299 @default.
• W4317829683 creator A5036841737 @default.
• W4317829683 creator A5043030979 @default.
• W4317829683 creator A5045322540 @default.
• W4317829683 creator A5048629507 @default.
• W4317829683 creator A5049918075 @default.
• W4317829683 creator A5061700482 @default.
• W4317829683 creator A5062422034 @default.
• W4317829683 creator A5070904867 @default.
• W4317829683 creator A5084158192 @default.
• W4317829683 creator A5086798464 @default.
• W4317829683 creator A5090294772 @default.
• W4317829683 creator A5090670583 @default.
• W4317829683 date "2023-01-24" @default.
• W4317829683 modified "2023-10-17" @default.
• W4317829683 title "CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa" @default.
• W4317829683 cites W1825622469 @default.
• W4317829683 cites W2212183969 @default.
• W4317829683 cites W2615089059 @default.
• W4317829683 cites W2792680957 @default.
• W4317829683 cites W2894373629 @default.
• W4317829683 cites W2916660491 @default.
• W4317829683 cites W2920530951 @default.
• W4317829683 cites W2971609950 @default.
• W4317829683 cites W2979544789 @default.
• W4317829683 cites W3024270563 @default.
• W4317829683 cites W3028844636 @default.
• W4317829683 cites W3042634019 @default.
• W4317829683 cites W3081828681 @default.
• W4317829683 cites W3092268290 @default.
• W4317829683 cites W3093384529 @default.
• W4317829683 cites W3119400137 @default.
• W4317829683 cites W3163978266 @default.
• W4317829683 cites W3164102285 @default.
• W4317829683 cites W3208430225 @default.
• W4317829683 cites W4210498497 @default.
• W4317829683 cites W4210992315 @default.
• W4317829683 doi "https://doi.org/10.1093/bjd/ljad013" @default.
• W4317829683 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36691791" @default.
• W4317829683 hasPublicationYear "2023" @default.
• W4317829683 type Work @default.
• W4317829683 citedByCount "3" @default.
• W4317829683 countsByYear W43178296832023 @default.
• W4317829683 crossrefType "journal-article" @default.
• W4317829683 hasAuthorship W4317829683A5000222857 @default.
• W4317829683 hasAuthorship W4317829683A5003966117 @default.
• W4317829683 hasAuthorship W4317829683A5014102803 @default.
• W4317829683 hasAuthorship W4317829683A5014721642 @default.
• W4317829683 hasAuthorship W4317829683A5021107172 @default.
• W4317829683 hasAuthorship W4317829683A5028901693 @default.
• W4317829683 hasAuthorship W4317829683A5031203411 @default.
• W4317829683 hasAuthorship W4317829683A5035608299 @default.
• W4317829683 hasAuthorship W4317829683A5036841737 @default.
• W4317829683 hasAuthorship W4317829683A5043030979 @default.
• W4317829683 hasAuthorship W4317829683A5045322540 @default.
• W4317829683 hasAuthorship W4317829683A5048629507 @default.
• W4317829683 hasAuthorship W4317829683A5049918075 @default.
• W4317829683 hasAuthorship W4317829683A5061700482 @default.
• W4317829683 hasAuthorship W4317829683A5062422034 @default.
• W4317829683 hasAuthorship W4317829683A5070904867 @default.
• W4317829683 hasAuthorship W4317829683A5084158192 @default.
• W4317829683 hasAuthorship W4317829683A5086798464 @default.
• W4317829683 hasAuthorship W4317829683A5090294772 @default.
• W4317829683 hasAuthorship W4317829683A5090670583 @default.
• W4317829683 hasBestOaLocation W43178296831 @default.
• W4317829683 hasConcept C126322002 @default.
• W4317829683 hasConcept C14942488 @default.
• W4317829683 hasConcept C203014093 @default.
• W4317829683 hasConcept C203565725 @default.
• W4317829683 hasConcept C2776317360 @default.
• W4317829683 hasConcept C2776694085 @default.
• W4317829683 hasConcept C2776914184 @default.
• W4317829683 hasConcept C2777063308 @default.
• W4317829683 hasConcept C2777767877 @default.
• W4317829683 hasConcept C2777983669 @default.
• W4317829683 hasConcept C71924100 @default.
• W4317829683 hasConcept C74133956 @default.
• W4317829683 hasConcept C90924648 @default.
• W4317829683 hasConceptScore W4317829683C126322002 @default.
• W4317829683 hasConceptScore W4317829683C14942488 @default.
• W4317829683 hasConceptScore W4317829683C203014093 @default.
• W4317829683 hasConceptScore W4317829683C203565725 @default.
• W4317829683 hasConceptScore W4317829683C2776317360 @default.
• W4317829683 hasConceptScore W4317829683C2776694085 @default.
• W4317829683 hasConceptScore W4317829683C2776914184 @default.
• W4317829683 hasConceptScore W4317829683C2777063308 @default.
• W4317829683 hasConceptScore W4317829683C2777767877 @default.
• W4317829683 hasConceptScore W4317829683C2777983669 @default.
• W4317829683 hasConceptScore W4317829683C71924100 @default.

• next