Cerebrospinal Fluid Biomarkers in Neurosarcoidosis: Evaluating the IL-2 and IL-6 Pathways
Susana Dominguez Penuela1, Greer Waldrop3, Maria Reyes-Mantilla1, David Acero-Garces1, Paula Barreras4, Evan Johnson1, H. Benjamin Larman2, Samuel Pleasure3, Kathryn Fitzgerald1, Michael Wilson3, Barney Stern1, Jeffrey Gelfand3, Carlos Pardo-Villamizar1
1Department of Neurology, 2Department of Pathology, Johns Hopkins University School of Medicine, 3Department of Neurology, University of California San Francisco, 4Department of Neurology, Cedars-Sinai Medical Center
Objective:
To assess levels of cerebrospinal fluid (CSF) cytokines associated with interleukins IL-2 and IL-6 pathways in patients with neurosarcoidosis (NS) and compare them with systemic sarcoidosis without neurological involvement (SS), inflammatory, and non-inflammatory controls (NIC).
Background:
Sarcoidosis is a systemic granulomatous disorder that affects the central or peripheral nervous system (CNS or PNS) in 5-25% of patients. Overlapping features with other conditions make diagnosis of NS difficult, highlighting the need for less invasive biomarkers.
Design/Methods:
We measured CSF levels of IL-2, IL-6 and their receptors, soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble interleukin-6 receptor (sIL-6R) using an immune-based multiplexed bead arrays (Luminex) and an automated immunoassay system (ELLA; Bio-Techne). Patients with probable and definite NS with clinical evidence of active disease (e.g., abnormal MRI and/or CSF findings), SS, multiple sclerosis (MS), cryptococcal meningitis (CM), and NIC were included. Statistical analyses were performed using GraphPad Prism Version 10.3.1, with significance set at p < 0.05.
Results:
Forty CSF samples were analyzed: 9 from NS patients, 8 each from SS, MS, NIC, and 7 from CM. Fifty-six percent of NS patients were male and African-American, with a median age of 44 years (IQR 34-58). ELLA showed greater sensitivity than Luminex for sIL-2Rα detection. sIL-2Rα levels were significantly higher in NS compared with SS, MS, and NIC while IL-2 levels were undetectable. NS patients also had significantly higher levels of IL-6 compared to SS and NIC, though sIL-6R levels were elevated only in CM compared to NS.
Conclusions:
Elevated CSF IL-6 and sIL-2Rα levels may serve as useful biomarkers to distinguish NS from other conditions, potentially reducing the reliance on invasive diagnostic procedures such as biopsy. Further validation in larger cohorts is necessary to confirm their clinical utility and assess correlations with patient outcomes.
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