frontier-banner
Frontiers
Home>Frontiers>

Annals of Neurology | Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis Reveal Novel Diagnostic and Immunopathological Insights

Annals of Neurology | Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis Reveal Novel Diagnostic and Immunopathological Insights
--

This study systematically analyzed cerebrospinal fluid cytokine and chemokine profiles in patients with central nervous system sarcoidosis, providing reliable biomarker data that facilitates differential diagnosis, disease activity assessment, and optimization of therapeutic strategies.

 

Literature Overview
This article, titled 'Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights' published in the Annals of Neurology, reviews and summarizes cytokine and chemokine profiles in central nervous system sarcoidosis patients. It compares these profiles with those of multiple sclerosis, primary central nervous system lymphoma, and AQP4-IgG-positive patients, offering novel biomarker clues for early diagnosis and immunological mechanisms exploration.

Background Knowledge
Neurosarcoidosis represents a subtype of sarcoidosis affecting the central nervous system. Its diagnosis remains challenging due to overlapping clinical manifestations and imaging features with other neurological conditions including multiple sclerosis and central nervous system lymphomas. Current treatment primarily relies on high-dose corticosteroids, with limited responses to TNF-α inhibitors, necessitating identification of more effective therapeutic targets. The research team employed a multiplex immunoassay system to comprehensively evaluate 17 cytokines and chemokines in cerebrospinal fluid, validating their potential roles in disease activity, diagnosis, and treatment response. This study highlights the superiority of cerebrospinal fluid over serum for detecting disease biomarkers, supporting further exploration of IL-6 and JAK inhibitors in neurosarcoidosis.

 

 

Research Methods and Experiments
The study employed a case-control design, enrolling 32 neurosarcoidosis patients (diagnosed at Mayo Clinic between January 2011 and February 2023) and multiple control groups including multiple sclerosis, primary central nervous system lymphoma, and AQP4-IgG-positive patients. Seventeen cytokines and chemokines in cerebrospinal fluid and serum were measured using the ELLA system. Protein levels were compared across groups to assess correlations with disease activity, imaging features, and therapeutic responses.

Key Conclusions and Perspectives

  • Neurosarcoidosis patients showed significant elevations in cerebrospinal fluid levels of IL-2, IL-6, IL-10, IL-13, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, IFN-γ, and TNF-α, with the most pronounced increases observed for IFN-γ, TNF-α, and GM-CSF.
  • 81% of neurosarcoidosis patients exhibited elevated cerebrospinal fluid TNF-α, 74% showed GM-CSF elevation, and 65% had increased CXCL9, with significantly higher frequency of elevation in cerebrospinal fluid compared to serum.
  • 61% of neurosarcoidosis patients demonstrated simultaneous increases in GM-CSF and CXCL9, whereas only one control subject showed this pattern.
  • Elevated levels of IL-6, CXCL9, CXCL10, GM-CSF, IFN-γ, and TNF-α correlated with neurological disease activity, indicating their potential as disease activity biomarkers.
  • GM-CSF and IL-13 elevations were absent in primary central nervous system lymphoma patients, while BAFF and IL-13 remained normal in multiple sclerosis patients, suggesting these factors serve as neurosarcoidosis-specific diagnostic markers.

Research Significance and Prospects
This study defines the cytokine and chemokine signature in neurosarcoidosis cerebrospinal fluid, revealing their potential applications in diagnosis, disease activity evaluation, and therapeutic target identification. Future studies should examine longitudinal samples to assess biomarker utility in disease prognosis. The findings particularly highlight IL-6 and JAK pathways as promising therapeutic targets, providing theoretical foundations for targeted treatments. Additionally, the GM-CSF/CXCL9 combination is recommended for improving diagnostic specificity in differential diagnosis scenarios.

 

 

Conclusion
In summary, this systematic evaluation of cerebrospinal fluid cytokine and chemokine profiles in neurosarcoidosis patients identified significant elevations of IL-6, IFN-γ, TNF-α, GM-CSF, CXCL9, and CXCL10 that correlate with disease activity. These biomarkers demonstrate substantial value for neurosarcoidosis diagnosis, therapeutic decision-making, and prognosis assessment. The study emphasizes cerebrospinal fluid's superiority over serum for detecting neuroinflammatory states, establishing a robust analytical framework for future research. Longitudinal analysis of these markers in follow-up studies could enhance prediction of disease recurrence or treatment response. Importantly, the findings suggest IL-6 and JAK inhibitors as potential novel therapeutic strategies, providing critical theoretical support for clinical translation.

 

Reference:
Georgios Mangioris, Sean J Pittock, Binxia Yang, Allen J Aksamit, and Anastasia Zekeridou. Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights. Annals of neurology.