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Published on: February 28, 2021
Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis
Levente Szalardy1, Denes Zadori, Ervin Tanczos
1Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.
Abstract:
Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcriptional factor involved in the regulation of glucose and lipid metabolism, has gained interest as a potential therapeutic target in multiple sclerosis (MS) due to its potent immunoregulatory properties and the therapeutic efficacy of its ligands in experimental autoimmune encephalitis (EAE). Elevated expression of PPARγ has been observed in the spinal cord of EAE mice and in an in vitro model of antigen-induced demyelination; however, no reports have yet been available on the PPARγ status in the central nervous system of human individuals with MS. Aiming to identify a possible alteration, the present study assessed the levels of PPARγ protein in the cerebrospinal fluid (CSF) of MS patients via ELISA technique. We report a pronounced elevation in the CSF levels of PPARγ in MS patients (n=35) compared to non-inflammatory controls (n=22). This elevation was independent of blood-CSF barrier integrity, but correlated with CSF white blood cell count and IgG index, associating the observed elevation with neuroinflammation. Controlling for potential confounders, the CSF levels of PPARγ further displayed a moderate but significant association with clinical severity. Corroborating with prior experimental findings, these results may contribute to our understanding about the role of PPARγ in MS, and may implicate this protein as a potential CSF biomarker of the disease.
Insights
Levels of peroxisome proliferator-activated receptor gamma (PPARγ) are elevated in the cerebrospinal fluid of multiple sclerosis patients, correlating with disease activity and severity. This suggests PPARγ may serve as a potential biomarker for MS neuroinflammation.
Area of Science:
- Neuroimmunology
- Metabolic regulation
- Biomarker discovery
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) regulates glucose/lipid metabolism and possesses immunomodulatory properties.
- PPARγ ligands show efficacy in experimental autoimmune encephalitis (EAE), a model for multiple sclerosis (MS).
- Previous studies noted elevated PPARγ in EAE spinal cords and demyelination models, but its status in human MS central nervous system (CNS) remained uncharacterized.
Purpose of the Study:
- To investigate the levels of PPARγ protein in the cerebrospinal fluid (CSF) of MS patients.
- To determine if PPARγ levels correlate with disease activity, neuroinflammation markers, or clinical severity in MS.
- To explore the potential of PPARγ as a CSF biomarker for MS.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify PPARγ protein levels in CSF.
- CSF samples were collected from MS patients (n=35) and non-inflammatory controls (n=22).
- Analysis included assessment of blood-CSF barrier integrity, CSF white blood cell count, IgG index, and clinical severity correlations.
Main Results:
- CSF levels of PPARγ were significantly elevated in MS patients compared to controls.
- The elevation in PPARγ was independent of blood-CSF barrier integrity.
- PPARγ levels correlated with CSF white blood cell count and IgG index, indicating a link to neuroinflammation, and showed a significant association with clinical severity.
Conclusions:
- The study demonstrates elevated CSF PPARγ levels in MS patients, associated with neuroinflammation and clinical severity.
- These findings support the role of PPARγ in MS pathogenesis and suggest its potential as a novel CSF biomarker for the disease.
- Further research is warranted to elucidate the precise mechanisms and therapeutic implications of PPARγ in MS.
