{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:34:36Z","timestamp":1790026476025,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T00:00:00Z","timestamp":1457395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100013956","name":"Black Country Comprehensive Local Research Network","doi-asserted-by":"crossref","award":["ID 14\/WM\/1175"],"award-info":[{"award-number":["ID 14\/WM\/1175"]}],"id":[{"id":"10.13039\/100013956","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J500434\/1"],"award-info":[{"award-number":["MR\/J500434\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Papillon-Lef\u00e9vre syndrome is a rare, inherited, autosomal-recessive disease, characterized by palmoplantar keratosis and severe prepubertal periodontitis, leading to premature loss of all teeth. Papillon-Lef\u00e9vre syndrome is caused by a mutation in the cathepsin C gene, resulting in complete loss of activity and subsequent failure to activate immune response proteins. Periodontitis in Papillon-Lef\u00e9vre syndrome is thought to arise from failure to eliminate periodontal pathogens as a result of cathepsin C deficiency, although mechanistic pathways remain to be elucidated. The aim of this study was to characterize comprehensively neutrophil function in Papillon-Lef\u00e9vre syndrome. Peripheral blood neutrophils were isolated from 5 patients with Papillon-Lef\u00e9vre syndrome, alongside matched healthy control subjects. For directional chemotactic accuracy, neutrophils were exposed to the chemoattractants MIP-1\u03b1 and fMLP and tracked by real-time videomicroscopy. Reactive oxygen species generation was measured by chemiluminescence. Neutrophil extracellular trap formation was assayed fluorometrically, and proinflammatory cytokine release was measured following overnight culture of neutrophils with relevant stimuli. Neutrophil serine protease deficiencies resulted in a reduced ability of neutrophils to chemotax efficiently and an inability to generate neutrophil extracellular traps. Neutrophil extracellular trap-bound proteins were also absent in Papillon-Lef\u00e9vre syndrome, and Papillon-Lef\u00e9vre syndrome neutrophils released higher levels of proinflammatory cytokines in unstimulated and stimulated conditions, and plasma cytokines were elevated. Notably, neutrophil chemoattractants MIP-1\u03b1 and CXCL8 were elevated in Papillon-Lef\u00e9vre syndrome neutrophils, as was reactive oxygen species formation. We propose that relentless recruitment and accumulation of hyperactive\/reactive neutrophils (cytokines, reactive oxygen species) with increased tissue transit times into periodontal tissues, alongside a reduced antimicrobial capacity, create a locally destructive chronic inflammatory cycle in Papillon-Lef\u00e9vre syndrome.<\/jats:p>","DOI":"10.1189\/jlb.5a1015-489r","type":"journal-article","created":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T03:33:44Z","timestamp":1457494424000},"page":"433-444","source":"Crossref","is-referenced-by-count":93,"title":["Characterization of neutrophil function in Papillon-Lef\u00e8vre syndrome"],"prefix":"10.1093","volume":"100","author":[{"given":"Helen","family":"Roberts","sequence":"first","affiliation":[{"name":"Periodontal Research Group and Medical Research Council-Centre for Immune Regulation, School of Dentistry, University of Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipa","family":"White","sequence":"additional","affiliation":[{"name":"Periodontal Research Group and Medical Research Council-Centre for Immune Regulation, School of Dentistry, University of Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irundika","family":"Dias","sequence":"additional","affiliation":[{"name":"Aston Research Centre for Healthy Ageing, School of Life and Health Sciences, Aston University , Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"McKaig","sequence":"additional","affiliation":[{"name":"Department of Dental Specialties Birmingham Children\u2019s Hospital National Health Service Foundation Trust , Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna","family":"Veeramachaneni","sequence":"additional","affiliation":[{"name":"School of Dentistry, The University of Manchester , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalin","family":"Thakker","sequence":"additional","affiliation":[{"name":"School of Dentistry, The University of Manchester , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Grant","sequence":"additional","affiliation":[{"name":"Periodontal Research Group and Medical Research Council-Centre for Immune Regulation, School of Dentistry, University of Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Chapple","sequence":"additional","affiliation":[{"name":"Periodontal Research Group and Medical Research Council-Centre for Immune Regulation, School of Dentistry, University of Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,8]]},"reference":[{"key":"2023011710413711100_B1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.tripleo.2009.03.016","article-title":"Papillon-Lefevre syndrome: clinical presentation and a brief review","volume":"108","author":"Dhanrajani","year":"2009","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"2023011710413711100_B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12104","article-title":"Molecular aspects of the pathogenesis of periodontitis","volume":"69","author":"Meyle","year":"2015","journal-title":"Periodontol. 2000"},{"key":"2023011710413711100_B3","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1600-0757.1994.tb00029.x","article-title":"Papillon-Lef\u00e8vre syndrome","volume":"6","author":"Hart","year":"1994","journal-title":"Periodontol. 2000"},{"key":"2023011710413711100_B4","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.4049\/jimmunol.173.12.7277","article-title":"Papillon-Lef\u00e8vre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C\/dipeptidyl peptidase I deficiency in humans","volume":"173","author":"Pham","year":"2004","journal-title":"J. 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