Observational studyNeurology(R) neuroimmunology & neuroinflammation2026
CSF Leukocytes Transiently Increase Before Onset of Huntington Disease in Association With a Stage-Specific CSF Cytokine/Chemokine Pattern.
Observational study in Neurology(R) neuroimmunology & neuroinflammation, 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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Abstract
BACKGROUND AND
objectivesCSF inflammatory biomarkers in Huntington disease (HD), a neurodegenerative CAG-triplet expansion disorder, usually increase with disease progression. CSF leukocytes as an inflammatory marker have not been explored in HD. We explored high-precision CSF-leukocyte counts across different HD stages in the multicenter prospective biosample HD study HDClarity and their association with CSF neurofilament light chain (NFL) and cytokine and chemokine patterns.
methodsA cross-sectional case-control study of the first average CSF leukocyte count of HDClarity study control participants (N = 94) and those carrying a repeat-expanded Huntingtin (
resultsCSF leukocytes peaked in late premanifest (median, interquartile range: 1.0/µL, 0.33-1.33/µL) when compared with early premanifest (0.0/µL, 0.0-1.0/µL) but also early (0.33/µL, 0.0-1.0/µL) and late manifest HD (0.0/µL, 0.0-0.67/µL). CSF leukocytes in late premanifest HD were higher than in controls (0.0/µL, 0.0-1.0/µL). A CSF-leukocyte peak at a DBS between 256 and 344 closely corresponded to the late premanifest HD peak. Higher CSF leukocytes in late premanifest HD were associated with higher CSF-NFL levels. Exploratory analysis of CSF cytokine and chemokine levels revealed that low interleukin (IL)-7 but high vascular endothelial growth factor (VEGF) and C-C motif chemokine ligand (CCL)22 levels may distinguish HD from control CSF; high VEGF, IL-6, and IL-15 early from late premanifest HD CSF; and low CCL2, CCL17, and IL-8 late premanifest from manifest HD CSF. When consecutively applied, these patterns identified late premanifest HD participants with a 75% sensitivity (95% CI 41%-96%) and 90% specificity (78%-96%). DISCUSSION: CSF leukocytes peaking in late premanifest HD, their association with increased CSF-NFL, and the corresponding stage-specific chemokine/cytokine changes indicate a temporally dynamic, probably neurotoxic inflammatory signaling network in HD.
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