Proteomic Profiling in Multiple Sclerosis Clinical Courses Reveals Potential Biomarkers of Neurodegeneration

Abstract

The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000–25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis

“…We used surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry to analyse serial serum samples from the population that participated in the MS-STAT study (described below) 1 , to identify proteins whose abundance was associated with MRI-measured brain atrophy rate. Serum proteomics in MS has previously been investigated in small cross-sectional studies to compare relapsing MS and progressive disease 10–12 . However, these previous studies were neither designed nor powered to identify correlates of neurodegeneration in SPMS.…”

Serum levels of chromogranins and secretogranins correlate with the progress and severity of Parkinson's disease

“…Granins are the major proteins in the core of secretory granules, where they may account for up to 80% of the total core proteins. Cgs and Sgs are involved in gastrointestinal endocrine tumors, neuroendocrine tumors, metabolic disease, and cardiovascular disease . Currently, it is not known whether the granin family plays a role in neurodegenerative diseases such as PD.…”

“…Cgs and Sgs are involved in gastrointestinal endocrine tumors, neuroendocrine tumors, metabolic disease, and cardiovascular disease. [19][20][21] Currently, it is not known whether the granin family plays a role in neurodegenerative diseases such as PD. Here, we investigated the correlation between serum levels of three granins (CgA, CgB, and SgII) and PD severity.…”

Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

“…Since low level of endogenous Tα1 is present in sera of patients affected with chronic inflammatory autoimmune diseases such as psoriatic arthritis, RA and SLE (Pica et al, 2016) as well as in RRMS patients (Giacomini et al, 2017), an interesting approach might also be to quantify the levels of serum Tβ4 in the same categories of patients to investigate whether a deregulation of both these thymic peptides may be related to MS-associated autoimmune responses. Tβ4 level in the MS population has been reported to be down-regulated in CSF (Liguori et al, 2014) and this down-regulation is a potential biomarker of MS.…”