{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:17:12Z","timestamp":1784661432289,"version":"3.55.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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 &amp;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 \u00d7 109 L\u20131, respectively; P = 8.8 \u00d7 10\u20134). 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\u20131, 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljad013","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T08:54:27Z","timestamp":1674550467000},"page":"636-648","source":"Crossref","is-referenced-by-count":18,"title":["CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa"],"prefix":"10.1093","volume":"188","author":[{"given":"Cristina","family":"Gamell","sequence":"first","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Bankovacki","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Scalzo-Inguanti","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Sedgmen","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monther","family":"Alhamdoosh","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Gail","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Turkovic","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Millar","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Johnson","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Wahlsten","sequence":"additional","affiliation":[{"name":"MD Biosciences, aka MLM Medical Labs Minnesota, Inc. , Oakdale, MN 55128 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Richter","sequence":"additional","affiliation":[{"name":"MD Biosciences, aka MLM Medical Labs Minnesota, Inc. , Oakdale, MN 55128 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Schuster","sequence":"additional","affiliation":[{"name":"MD Biosciences, aka MLM Medical Labs Minnesota, Inc. , Oakdale, MN 55128 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Dyson","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Nicolopoulos","sequence":"additional","affiliation":[{"name":"Dermatology Department, Royal Melbourne Hospital , Parkville, VIC 3050 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Varigos","sequence":"additional","affiliation":[{"name":"Dermatology Department, Royal Melbourne Hospital , Parkville, VIC 3050 , Australia"},{"name":"Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne , Carlton VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Ng","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Wilson","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Field","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes S","family":"Kern","sequence":"additional","affiliation":[{"name":"Dermatology Department, Royal Melbourne Hospital , Parkville, VIC 3050 , Australia"},{"name":"Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne , Carlton VIC , Australia"},{"name":"Department of Medicine, Central Clinical School, Monash University , Melbourne, VIC , Australia"},{"name":"Department of Dermatology, Alfred Hospital , Melbourne, VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Lindqvist","sequence":"additional","affiliation":[{"name":"CSL Innovation , Melbourne, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"2023100619301243700_ljad013-B1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/ajd.12766","article-title":"Hidradenitis suppurativa, a review of pathogenesis, associations and management. 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