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

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

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.

Keywords: Adiponectin; Cerebrospinal fluid; HMW oligomers; Inflammation; Multiple sclerosis.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
ELISA showed that total CSF adiponectin levels were significantly higher in MS patients than in controls (9.91 ± 7.53 vs 6.02 ± 2.74, p value = 0.009)
Fig. 2
Fig. 2
CSF adiponectin directly correlates with CSF IgG
Fig. 3
Fig. 3
Adiponectin high molecular weight (HMW) and medium molecular weight (MMW) oligomers are significantly higher in patients with multiple sclerosis (MS) than in controls. a Representative Western blot for total adiponectin and its different oligomers [HMW, MMW, low molecular weight (LMW)] in the serum of five controls and five patients with MS. b Pixel quantization of all controls and all patients with MS. Values are reported as percentages compared with the control. *P < 0.05
Fig. 4
Fig. 4
Adiponectin oligomers are increased in CSF from MS patients compared with normal controls. Adiponectin oligomers in each fraction obtained from fast protein liquid chromatography analysis and subjected to ELISA (a) and Western blotting (b)

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