{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:37Z","timestamp":1792788577890,"version":"4.5.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2016-00982"],"award-info":[{"award-number":["2016-00982"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2019-01123"],"award-info":[{"award-number":["2019-01123"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"hj\u00e4rt-lungfonden","doi-asserted-by":"publisher","award":["20180218"],"award-info":[{"award-number":["20180218"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004392","name":"stiftelsen patentmedelsfonden f\u00f6r odontologisk profylaxforskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TUA Research Funding","award":["TUAGBG-917531"],"award-info":[{"award-number":["TUAGBG-917531"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Papillon-Lef\u00e8vre Syndrome (PLS) is an autosomal recessive monogenic disease caused by loss-of-function mutations in the\n                    <jats:italic>CTSC<\/jats:italic>\n                    gene, thus preventing the synthesis of the protease Cathepsin C (CTSC) in a proteolytically active form. CTSC is responsible for the activation of the pro-forms of the neutrophil serine proteases (NSPs; Elastase, Proteinase 3 and Cathepsin G), suggesting its involvement in a variety of neutrophil functions. In PLS neutrophils, the lack of CTSC protease activity leads to inactivity of the NSPs. Clinically, PLS is characterized by an early, typically pre-pubertal, onset of severe periodontal pathology and palmoplantar hyperkeratosis. However, PLS is not considered an immune deficiency as patients do not typically suffer from recurrent and severe (bacterial and fungal) infections. In this study we investigated an unusual\n                    <jats:italic>CTSC<\/jats:italic>\n                    mutation in two siblings with PLS, a 503A&gt;G substitution in exon 4 of the\n                    <jats:italic>CTSC<\/jats:italic>\n                    gene, expected to result in an amino acid replacement from tyrosine to cysteine at position 168 of the CTSC protein. Both patients bearing this mutation presented with pronounced periodontal pathology. The characteristics and functions of neutrophils from patients homozygous for the 503A&gt;G\n                    <jats:italic>CTSC<\/jats:italic>\n                    mutation were compared to another previously described PLS mutation (755A&gt;T), and a small cohort of healthy volunteers. Neutrophil lysates from patients with the 503A&gt;G substitution lacked CTSC protein and did not display any CTSC or NSP activity, yet neutrophil counts, morphology, priming, chemotaxis, radical production, and regulation of apoptosis were without any overt signs of alteration. However, NET formation upon PMA-stimulation was found to be severely depressed, but not abolished, in PLS neutrophils.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0261724","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T13:44:27Z","timestamp":1640094267000},"page":"e0261724","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["A rare CTSC mutation in Papillon-Lef\u00e8vre Syndrome results in abolished serine protease activity and reduced NET formation but otherwise normal neutrophil function"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0166-5875","authenticated-orcid":true,"given":"Felix P.","family":"Sanchez Klose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halla","family":"Bj\u00f6rnsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Dahlstrand Rudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tishana","family":"Persson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arsham","family":"Khamzeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Sundqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Thorbert-Mros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gis","family":"Dieckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Christenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-6478","authenticated-orcid":true,"given":"Johan","family":"Bylund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"pone.0261724.ref001","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nri3399","article-title":"Neutrophil recruitment and function in health and inflammation","volume":"13","author":"E. 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Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0261724","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T13:46:04Z","timestamp":1699969564000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0261724"}},"subtitle":[],"editor":[{"given":"Charaf","family":"Benarafa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,21]]},"references-count":55,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0261724","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,21]]}}}