4.7 Article

Neuroinflammation Is Associated with GFAP and sTREM2 Levels in Multiple Sclerosis

Journal

BIOMOLECULES
Volume 12, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/biom12020222

Keywords

multiple sclerosis (MS); neuroinflammation; neurodegeneration; microglia; astroglia; soluble triggering receptor expressed on myeloid cells-2 (sTREM-2); glial fibrillary acid protein (GFAP); cytokines; cerebrospinal fluid (CSF) biomarkers

Funding

  1. FISM grants (Fondazione Italiana Sclerosi Multipla) [2019/S/1]
  2. Italian Ministry of Universities and Research [2017K55HLC]
  3. Italian Ministry of Health [RF-2018-12366144]
  4. Fondazione Italiana Sclerosi Multipla (FISM) [2018/S/5]
  5. Ministero della Salute [GR-2016-02363725, RF-2019-12371111]
  6. Progetti di Rilevante Interesse Nazionale (PRIN) [2017K55HLC 001]
  7. National Research Council

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The study found that GFAP and sTREM-2 are suitable biomarkers for central inflammation in multiple sclerosis (MS) and are associated with certain inflammatory factors and clinical characteristics. Enhanced CSF expression of GFAP may indicate a higher risk of progression in patients.
Background: Astrocytes and microglia play an important role in the inflammatory process of multiple sclerosis (MS). We investigated the associations between the cerebrospinal fluid (CSF) levels of glial fibrillary acid protein (GFAP) and soluble triggering receptors expressed on myeloid cells-2 (sTREM-2), inflammatory molecules, and clinical characteristics in a group of patients with relapsing-remitting MS (RRMS). Methods: Fifty-one RRMS patients participated in the study. Clinical evaluation and CSF collection were performed at the time of diagnosis. The CSF levels of GFAP, sTREM-2, and of a large set of inflammatory and anti-inflammatory molecules were determined. MRI structural measures (cortical thickness, T2 lesion load, cerebellar volume) were examined. Results: The CSF levels of GFAP and sTREM-2 showed significant correlations with inflammatory cytokines IL-8, G-CSF, and IL-5. Both GFAP and sTREM-2 CSF levels positively correlated with age at diagnosis. GFAP was also higher in male MS patients, and was associated with an increased risk of MS progression, as evidenced by higher BREMS at the onset. Finally, a negative association was found between GFAP CSF levels and cerebellar volume in RRMS at diagnosis. Conclusions: GFAP and sTREM-2 represent suitable biomarkers of central inflammation in MS. Our results suggest that enhanced CSF expression of GFAP may characterize patients with a higher risk of progression.

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