ArticleHemaSphere2026
Targeted proteomics reveal histiocytosis-associated neurodegeneration signatures.
Article in HemaSphere, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
30 authors.
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Abstract
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-LCH. 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-LCH exhibited a distinct CSF proteomic profile characterized by increased decoy receptors, including interleukin-1 receptor type 2 (IL-1RT2), macrophage activation markers, and cytotoxic and immunoregulatory proteins. CSF IL-1RT2 showed higher specificity for ND-LCH than CSF NFL (0.99 [0.99-1.0] vs. 0.88 [0.80-0.96]) and tracked longitudinal disease changes. Plasma analyses revealed a complementary immune signature in which NFL correlated with CSF markers, including IL-1RT2, and distinguished ND-LCH from controls. In independent plasma NFL cohorts from France and Japan, elevated levels were confirmed in adults with histiocytosis-associated ND. These findings define a neuroinflammatory signature of ND-LCH and identify IL-1RT2 as a novel candidate biomarker for diagnosis and monitoring.
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Registered trials
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