Neuroinflammation Is Associated with GFAP and sTREM2 Levels in Multiple Sclerosis.

Federica Azzolini,Mario Stampanoni Bassi,Antonio Bruno,Fabio Buttari,Ennio Iezzi,Luana Gilio,Teresa Micillo,Georgia Mandolesi,Ettore Dolcetti,Annamaria Finardi,Giuseppe Matarese,Fortunata Carbone,Alessandra Musella,Diego Centonze,Luigi Pavone,Livia Guadalupi,Roberto Furlan

doi:10.3390/biom12020222

Abstract

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.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by neuroinflammation and neurodegeneration often coexisting from the earliest stages of the disease
According to the idea that astroglia and microglial cells are activated in parallel and interact mutually, we found a strong correlation between glial fibrillary acid protein (GFAP) and soluble triggering receptors expressed on myeloid cells-2 (sTREM-2) Cerebrospinal fluid (CSF)
Consistent with the hypothesis that both microglia and astrocytes participate in the induction and maintenance of the inflammatory response in multiple sclerosis (MS), we found a strong positive correlation between CSF levels of GFAP and sTREM-2

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by neuroinflammation and neurodegeneration often coexisting from the earliest stages of the disease. Glial fibrillary acid protein (GFAP) and the soluble triggering receptor expressed on myeloid cells 2 (sTREM-2), two established biomarkers of astroglial and microglial activation, have been proposed as prognostic tools in MS [9,10,11,12] Both GFAP and sTREM-2 CSF and serum levels have been correlated with clinical disability and neuroradiological activity in MS [8,12,13,14]; serum levels of GFAP have been associated with a progressive course, higher EDSS, older age, longer disease duration [15]. 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). The CSF levels of GFAP, sTREM-2, and of a large set of inflammatory and anti-inflammatory molecules were determined.

Methods

Results

Conclusion