{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:56:27Z","timestamp":1790679387346,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100002136","name":"Histiocytosis Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurodegeneration (ND) is a severe complication of Langerhans cell histiocytosis (LCH), yet its underlying biology and reliable biomarkers remain poorly defined. The aim of this study was to (1) gain insight into neuroimmunological mechanisms governing ND and (2) assess the clinical value of established and novel biomarkers for ND\u2010LCH. We applied targeted proteomics and neurofilament light chain (NFL) assays to cerebrospinal fluid (CSF) and plasma from LCH patients with and without ND, with control cohorts. ND\u2010LCH exhibited a distinct CSF proteomic profile characterized by increased decoy receptors, including interleukin\u20101 receptor type 2 (IL\u20101RT2), macrophage activation markers, and cytotoxic and immunoregulatory proteins. CSF IL\u20101RT2 showed higher specificity for ND\u2010LCH than CSF NFL (0.99 [0.99\u20131.0] vs. 0.88 [0.80\u20130.96]) and tracked longitudinal disease changes. Plasma analyses revealed a complementary immune signature in which NFL correlated with CSF markers, including IL\u20101RT2, and distinguished ND\u2010LCH from controls. In independent plasma NFL cohorts from France and Japan, elevated levels were confirmed in adults with histiocytosis\u2010associated ND. These findings define a neuroinflammatory signature of ND\u2010LCH and identify IL\u20101RT2 as a novel candidate biomarker for diagnosis and monitoring.<\/jats:p>","DOI":"10.1002\/hem3.70470","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:31:39Z","timestamp":1788780699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted proteomics reveal histiocytosis\u2010associated neurodegeneration signatures"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-092X","authenticated-orcid":false,"given":"Egle","family":"Kvedaraite","sequence":"first","affiliation":[{"name":"Department of Pathology and Cancer Diagnostics Karolinska University Hospital Stockholm Sweden"},{"name":"Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet Stockholm 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