The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study

Nielsen, Helle Hvilsted; Beck, Hans Christian; Kristensen, Lars; Burton, Mark; Csépány, Tünde; Simó, Magdolna; Diószeghy, Péter; Sejbæk, Tobias; Grebing, Manuela; Heegaard, Niels H. H.; Illés, Zsolt

doi:10.1371/journal.pone.0139659

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…4 The diagnostic workup of MS comprise an anamnestic support for spreading of neurological symptoms, supported by magnetic resonance imaging (MRI) findings and levels of CSF/serum biomarkers such as an increased IgG index and the presence of oligoclonal bands (OCBs) in the CSF. To date, substantial efforts have been put into testing new candidate biomarker molecules in various body fluids from patients (e.g., serum/plasma, CSF, urine), 5,6 but given the complex nature of the disease, only a few candidate biomarkers have been considered as valid contributions to the diagnostic criteria of MS. 7,8 Consequently, a panel of biomarkers comprising multifactorial processes in inflammation and neuro-degeneration may hold the best promise for earlier diagnosis and prognosis, 7,9 especially with the objective of initiating the optimal disease modifying therapy as early as possible. 10 To this end, it is known that several key cell-surface receptors involved in regulating immune function are shed from the surfaces of immune cells via the activity of metalloproteinases.…”

Section: Introductionmentioning

confidence: 99%

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

et al. 2017

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Multiple sclerosis (MS) is an immune mediated, inflammatory and demyelinating disease of the central nervous system (CNS). Substantial evidence points toward monocytes and macrophages playing prominent roles early in disease, mediating both pro‐ and anti‐inflammatory responses. Monocytes are subdivided into three subsets depending on the expression of CD14 and CD16, representing different stages of inflammatory activation. To investigate their involvement in MS, peripheral blood mononuclear cells from 40 patients with incipient or progressed MS and 20 healthy controls were characterized ex vivo. In MS samples, we demonstrate a highly significant increase in nonclassical monocytes (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16−) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 was found, attributable to the upregulation of the nonclassical monocytes. In addition, significantly increased levels of human endogenous retrovirus (HERV) envelope (Env) epitopes, encoded by both HERV‐H/F and HERV‐W, were specifically found on nonclassical monocytes from patients with MS; emphasizing their involvement in MS disease. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed for soluble biomarkers of inflammation and neurodegeneration. For sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) population was found, as were correlations between levels of soluble osteopontin and the HERV Env expression on nonclassical monocytes. The results from this study emphasize the relevance of further focus on monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases.

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Section: Introductionmentioning

confidence: 99%

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

et al. 2017

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“…After centrifugation, proteins were dissolved in lysis buffer (8 M urea, 2 M thiourea, 25 mM dithiothreitol and 50 mM Tris). The urinary proteins were then denatured with dithiothreitol, alkylated with iodoacetamide and digested with trypsin (Promega) (1:50) at 37°C overnight using filter-aided sample preparation methods as previously described [12]. The digested peptides were desalted using Oasis HLB cartridges (Waters, USA).…”

Section: Methodsmentioning

confidence: 99%

“…MScl shares many overlapping clinical features with neuromyelitis optica spectrum disorders (NMO-SD), but the treatment strategies differ substantially for these two diseases, and misdiagnosis can often result in wrong treatment [11]. Several urinary proteomic/metabolic studies have been conducted to differentiate these two diseases [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Early urinary candidate biomarkers and clinical outcomes of intervention in a rat model of experimental autoimmune encephalomyelitis

Zhao

et al. 2017

Preprint

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Biomarker is the change associated with the disease. Without homeostatic control, urine can accumulate early changes in the body. We expect that urinary proteome can also reflect early changes in the nervous system and urine is a better biomarker source for nervous system diseases.Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system and is difficult to diagnose in early stages. In this study, a tandem mass labeling approach coupled with high-resolution mass spectrometry was used to analyze seven-day urinary proteome changes in a rat model of experimental autoimmune encephalomyelitis when the clinical scores in the EAE group were " 0" and no obvious histological changes were observed. Thirty-one urinary proteins were altered, based on Ingenuity Pathway Analysis, seventeen of these proteins were associated with neurological functions. The top canonical pathways represented by these dysregulated proteins included the acute phase response and metabolic processes. The acute phase response was characterized by an increase in inflammatory factors that are known to cause multiple sclerosis.Additionally, lipid or glucose metabolic alterations may provide clues for future mechanistic studies on multiple sclerosis. Fourteen proteins were identified to have catalytic activities that may contribute to neuronal damage. Furthermore, among the seven proteins that were most affected, six were reported to be expressed in the serum/cerebrospinal fluid/brain tissue of multiple sclerosis patients, thereby indicating that urine can be a good source of biomarkers for the early detection of multiple sclerosis.peer-reviewed)

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“…In a second study, Neilson et al. compared urine proteomes of NMO ( n = 32) to MS patients ( n = 46) using quantitative LC‐MS/MS after trypsin digestion and iTRAQ labeling and identified 1112 different proteins . In the future, larger clinical studies are required to verify and expand upon these results, as urine biomarkers could be the most convenient for clinical application if proven to be reliable.…”

Section: Application Of Proteomics To Identify Biomarkers For and Patmentioning

confidence: 99%

“…In addition to having secreted proteins from salivary glands, saliva also contains proteins from the gingival cervicular fluid, oral microflora, and also plasmatic proteins. Diagnostic tests on saliva are common and cost‐effective, particularly for patients who need to monitor their hormone levels or the effectiveness of ongoing therapies . The human saliva proteome has been profiled from healthy and disease cases .…”

Section: Application Of Proteomics To Identify Biomarkers For and Patmentioning

confidence: 99%

Proteomic Approaches to Decipher Mechanisms Underlying Pathogenesis in Multiple Sclerosis Patients

2019

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). The cause of MS is unknown, with no effective therapies available to halt the progressive neurological disability. Development of new and improvement of existing therapeutic strategies therefore require a better understanding of MS pathogenesis, especially during the progressive phase of the disease. This can be achieved through development of biomarkers that can help to identify disease pathophysiology and monitor disease progression. Proteomics is a powerful and promising tool to accelerate biomarker detection and contribute to novel therapeutics. In this review, an overview of how proteomic technology using CNS tissues and biofluids from MS patients has provided important clues to the pathogenesis of MS is provided. Current publications, pitfalls, as well as directions of future research involving proteomic approaches to understand the pathogenesis of MS are discussed.

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The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study

Cited by 18 publications

References 38 publications

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

Early urinary candidate biomarkers and clinical outcomes of intervention in a rat model of experimental autoimmune encephalomyelitis

Proteomic Approaches to Decipher Mechanisms Underlying Pathogenesis in Multiple Sclerosis Patients

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