Elevated serum growth differentiation factor 15 in multiple system atrophy patients: A case control study

Abstract

Background: Multiple system atrophy (MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15 (GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.

Aim: To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson's disease (PD) patients and healthy controls.

Methods: A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.

Results: Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively).

Conclusion: Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Keywords: Biomarker; Multiple system atrophy; Neurodegenerative disease; Parkinson’s disease; Receiver-operating characteristic curve; Serum growth differentiation factor 15.

Figure 1

The serum levels of growth differentiation factor 15 in multiple system atrophy-parkinsonian type patients, multiple system atrophy-cerebellar type patients and Parkinson disease patients. Serum growth differentiation factor 15 levels in multiple system atrophy-parkinsonian type patients and multiple system atrophy-cerebellar type patients were both significantly higher than those in Parkinson disease patients (P = 0.000, 0.000, respectively). MSA-P: Multiple system atrophy-parkinsonian type; MSA-C: Multiple system atrophy-cerebellar type; MSA: Multiple system atrophy; PD: Parkinson disease; GDF15: Growth differentiation factor 15.

Figure 2

Receiver-operating characteristic curve analysis of growth differentiation factor 15 for the diagnosis of multiple system atrophy. A: Total multiple system atrophy (MSA) patients vs total controls; B: Male MSA patients vs male controls; C: Female MSA patients vs female controls; D: Total MSA patients vs total Parkinson disease patients; E: Male MSA patients vs male Parkinson disease patients; F: Female MSA patients vs female controls. AUC: Area under the receiver-operating characteristic curve.