Adiponectin in Cerebrospinal Fluid from Patients Affected by Multiple Sclerosis Is Correlated with the Progression and Severity of Disease

Marcella Coletta,Maria Ludovica Monaco,Rita Polito,Marta Mallardo,Ersilia Nigro,Giacomo Lus,Fabiana Rossi,Elisabetta Signoriello,Aurora Daniele,Andrea Di Pietro,Sara Casertano

doi:10.1007/s12035-021-02287-z

Abstract

Adiponectin exerts relevant actions in immunity and is modulated in several disorders, such as multiple sclerosis (MS). In this study, we characterized adiponectin expression and profiles in cerebrospinal fluid (CSF) from MS patients to investigate its potential relationship with the severity and progression of the disease. Total adiponectin in CSF was measured by ELISA in 66 unrelated CSF MS patients and compared with 24 age- and sex-matched controls. Adiponectin oligomer profiles were analysed by Western blotting and FPLC chromatography. Total CSF adiponectin was significantly increased in MS patients compared with controls (9.91 ng/mL vs 6.02 ng/mL) (p < 0.001). Interestingly, CSF adiponectin positively correlated with CSF IgG, and CSF/serum albumin directly correlated with CSF/serum adiponectin. Our data demonstrated that CSF adiponectin predicts a worse prognosis: patients with the progressive form of MS had higher levels compared with the relapsing remitting form; patients with higher EDSS at baseline and a higher MS severity score at 4.5-year follow-up had significantly elevated adiponectin levels with respect to patients with a less severe phenotype. Finally, the adiponectin oligomerization profile was altered in CSF from MS patients, with a significant increase in HMW and MMW. The correlation of CSF adiponectin with the severity and prognosis of MS disease confirmed the role of this adipokine in the inflammatory/immune processes of MS and suggested its use as a complementary tool to assess the severity, progression and prognosis of the disease. Further studies on larger MS cohorts are needed to clarify the contribution of adiponectin to the etiopathogenesis of MS.

Highlights

The original online version of this article was revised: The surnames and givenames of authors were interchanged.Elisabetta Signoriello and Marta Mallardo contributed to this work.Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system (CNS) that is very often accompanied by unpredictable clinical relapses and remissions and/ or by disability progression over time
Using the univariate model and comparing the two MS patient subgroups, we found that patients with cerebrospinal fluid (CSF) adiponectin levels above the arbitrary cut-off had significantly higher body mass index (BMI), serum adiponectin, multiple sclerosis severity score (MSSS) and Expanded Disability Status Scale (EDSS) at the end of the 4.5-year follow-up
We found that CSF levels of adiponectin and its oligomers were increased in MS patients compared with control subjects matched for age, sex and BMI

Summary

Introduction

Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system (CNS) that is very often accompanied by unpredictable clinical relapses and remissions and/ or by disability progression over time. The aetiology remains unclear, but the main MS pathological features are due to inflammatory attacks that lead to neurodegenerative processes [1, 2]. Cerebrospinal fluid (CSF) protects the central nervous system (CNS) in different ways: regulation of metabolic homeostasis, supply of nutrients, adjuvant of the lymphatic system and regulation of intracranial pressure [3]. CSF represents the “gold standard” laboratory sample for the diagnosis of MS through the presence of oligoclonal bands, a symptom of CNS inflammation [4, 5]. The analysis of CSF markers permits the evaluation of inflammatory processes in MS [6]

Objectives

Methods

Results

Discussion

Conclusion