{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:01:49Z","timestamp":1790672509155,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"abstract":"\n Objective<\/jats:title>\n Chronic recurrent multifocal osteomyelitis (CRMO) is a pediatric autoinflammatory bone disease with poorly defined pathophysiology and limited biomarkers. Murine models implicate neutrophils, neutrophil\u2010derived IL\u20101\u03b2, and the adaptor protein PSTPIP2, but direct evidence in human CRMO is lacking. This study aims to translate findings from mouse models to human disease by investigating the role of neutrophils and PSTPIP2 in CRMO.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Blood samples from 34 patients with CRMO and 20 controls were analyzed by flow cytometry, biochemical assays, and transcriptomic profiling of purified neutrophils. Patients were evaluated across treatment groups (untreated, NSAIDs, zoledronate, or anti\u2010TNF therapy). Neutrophil activation, PSTPIP2 expression, inflammatory gene responses, and correlations with clinical parameters were assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CRMO neutrophils displayed chronic activation marked by reduced CD62L expression (p\u2010value p=0.0016; Mann Whitney test), which correlated with MRI lesion burden. PSTPIP2 protein levels were consistently decreased (p=0.0006) despite elevated mRNA expression (p=0.0005) and absence of coding mutations, suggesting inflammation\u2010associated post\u2010transcriptional regulation. Both neutrophil activation and PSTPIP2 downregulation normalized in patients receiving anti\u2010TNF therapy. Unlike murine models,\n IL1B<\/jats:italic>\n and\n CXCL8<\/jats:italic>\n expression were not increased. Transcriptomic profiling (4 patients and 3 controls) identified enrichment of NF\u2010\u03baB signaling, inflammatory and chemotaxis pathways, with upregulation of\n CCL4<\/jats:italic>\n ,\n CCL4L2<\/jats:italic>\n ,\n ATL1<\/jats:italic>\n ,\n VNN1<\/jats:italic>\n ,\n H2BC7<\/jats:italic>\n ,\n LINC02207<\/jats:italic>\n , and downregulation of\n ISL2<\/jats:italic>\n . Several transcripts correlated with clinical measures of disease burden.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n These findings identify neutrophil activation and inflammation\u2010sensitive PSTPIP2 deficiency as central features of human CRMO, suggest chemokines as potential biomarkers, and mechanistically explain why TNF blockade provides clinical benefit.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.70356","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:19:01Z","timestamp":1790669941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil\u2010Driven Inflammation in Pediatric Chronic Recurrent Multifocal Osteomyelitis"],"prefix":"10.1002","author":[{"given":"Nataliia","family":"Pavliuchenko","sequence":"first","affiliation":[{"name":"Laboratory of Leukocyte Signalling Institute of Molecular Genetics of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-2219","authenticated-orcid":false,"given":"Petr","family":"Dan\u011bk","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Analysis of Growth Regulation in Animals Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo namesti 542\/2 160 00 Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Malcov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adult Rheumatology Motol and Homolka University Hospital V Uvalu 84 150 06 Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-9990","authenticated-orcid":false,"given":"Rudolf","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adult Rheumatology Motol and Homolka University Hospital V Uvalu 84 150 06 Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dita","family":"Cebecauerov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adult Rheumatology Motol and Homolka University Hospital V Uvalu 84 150 06 Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1560-4398","authenticated-orcid":false,"given":"Tom\u00e1\u0161","family":"Brdi\u010dka","sequence":"additional","affiliation":[{"name":"Laboratory of Leukocyte Signalling Institute of Molecular Genetics of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70356","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:19:02Z","timestamp":1790669942000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":0,"alternative-id":["10.1002\/art.70356"],"URL":"https:\/\/doi.org\/10.1002\/art.70356","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.70356"}}