Proteomic analysis of rat tibialis anterior muscles at different stages of experimental autoimmune myasthenia gravis

Gomez, Alejandro M.; Vanheel, Annelies; Losen, Mario; Molenaar, Peter; Baets, Marc H. De; Noben, Jean-Paul; Hellings, Niels; Martínez‐Martínez, Pilar

doi:10.1016/j.jneuroim.2013.05.008

Cited by 11 publications

(4 citation statements)

References 27 publications

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“…To date, only few studies have dealt with identification of molecular markers in MG disease by proteomic analysis, but none of them used plasma-enriched samples to detect medium- and low-abundance proteins. 20 –22 By this approach, we documented a statistically significant reduction of plasma vitronectin expression in all MG patients subgroups as compared to healthy controls that did not correlate neither with the severity of the disease nor with the immunosuppressive therapy. Although it could represent a limitation of our study, vitronectin reduction in plasma of MG patients, described for the first time in this study, might be interesting and deserves further studies addressed to the evaluation of its relevance/roles in the pathogenesis or progression of MG disease.…”

Section: Discussionmentioning

confidence: 92%

Plasma vitronectin is reduced in patients with myasthenia gravis: Diagnostic and pathophysiological potential

Lepedda

Deiana

Lobina

et al. 2019

Journal of Circulating Biomarkers

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Myasthenia gravis (MG) is an autoimmune disease leading to varying degrees of skeletal muscle weakness. It is caused by specific antibodies directed against definite components in the postsynaptic membrane at the neuromuscular junction (NMJ), such as the acetylcholine receptor (AChR) and the muscle-specific kinase (MUSK) receptor. In clinical practice, MG patients may be classified into three main subgroups based on the occurrence of serum autoantibodies directed against AChR or MUSK receptor or antibody-negative. As the MG subgroups differ in terms of clinical characteristics, disease pathogenesis, prognosis, and response to therapies, they could benefit from targeted treatment as well as the detection of other possible disease biomarkers. We performed proteomics on plasma fractions enriched in low-abundance proteins to identify potential biomarkers according to different autoimmune responses. By this approach, we evidenced a significant reduction of vitronectin in MG patients compared to healthy controls, irrespective of the autoantibodies NMJ target. The obtained results were validated by mono- and two-dimensional Western blotting analysis. Vitronectin is a multifunctional glycoprotein involved in the regulation of several pathophysiological processes, including complement-dependent immune response, coagulation, fibrinolysis, pericellular proteolysis, cell attachment, and spreading. The pathophysiological significance of the reduction of plasma vitronectin in MG patients has yet to be fully elucidated. It could be related either to a possible deposition of vitronectin at NMJ to counteract the complement-mediated muscle damage at this level or to a parallel variation of this glycoprotein in the muscle extracellular matrix with secondary induced alteration in clustering of AChRs at NMJ, as it occurs with variation in concentrations of agrin, another extracellular matrix component. The clinical value of measuring plasma vitronectin has yet to be defined. According to present findings, significantly lower plasma values of this glycoprotein might be indicative of an impaired complement-dependent immune response.

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Section: Discussionmentioning

confidence: 92%

Plasma vitronectin is reduced in patients with myasthenia gravis: Diagnostic and pathophysiological potential

Lepedda

Deiana

Lobina

et al. 2019

Journal of Circulating Biomarkers

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“…In addition, proteomics was instrumental in the determination of key post-translational modifications in muscle proteins such as glycosylation [23], phosphorylation [24], carbonylation [25], nitrosylation [26] and acetylation [27]. The systematic proteomic screening of skeletal muscle pathologies has included the analysis of patient biopsy material and muscle preparations from established animal models of muscle diseases, covering neuromuscular abnormalities such as drug-related muscle damage [28], toxin-associated muscle alterations [29], denervationinduced muscular atrophy [30,31], motor neuron diseases [32][33][34], limb-girdle muscular dystrophy [35], hyper-excitability related myotonia [36], insulin resistance and diabetes-associated muscle weakness [37][38][39], obesity-related changes in muscle tissues [40,41], inclusion body myositis [42], autoimmune myasthenia gravis [43], dysferlinopathy [44], myofibrillar myopathies [45][46][47], and post-mortem changes in skeletal muscle [48]. In addition, the downstream effects of dystrophin deficiency were studied by various proteomic approaches [49].…”

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry-Based Identification of Muscle-Associated and Muscle-Derived Proteomic Biomarkers of Dystrophinopathies

Dowling

Holland

Ohlendieck

2014

Journal of Neuromuscular Diseases

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The optimization of large-scale screening procedures of pathological specimens by genomic, proteomic and metabolic methods has drastically increased the bioanalytical capability for swiftly identifying novel biomarkers of inherited disorders, such as neuromuscular diseases. X-linked muscular dystrophy represents the most frequently inherited muscle disease and is characterized by primary abnormalities in the membrane cytoskeletal protein dystrophin. Mass spectrometry-based proteomics has been widely employed for the systematic analysis of dystrophin-deficient muscle tissues, using patient samples and animal models of dystrophinopathy. Both, gel-based methods and label-free mass spectrometric techniques have been applied in comparative analyses and established a large number of altered proteins that are associated with muscle contraction, energy metabolism, ion homeostasis, cellular signaling, the cytoskeleton, the extracellular matrix and the cellular stress response. Although these new indicators of muscular dystrophy have increased our general understanding of the molecular pathogenesis of dystrophinopathy, their application as new diagnostic or prognostic biomarkers would require the undesirable usage of invasive methodology. Hence, to reduce the need for diagnostic muscle biopsy procedures, more recent efforts have focused on the proteomic screening of suitable body fluids, such as plasma, serum or urine, for the identification of changed concentration levels of muscle-derived peptides, protein fragments or intact proteins. The occurrence of muscular dystrophy-related protein species in biofluids will be extremely helpful for the future development of cost-effective and non-invasive diagnostic procedures. Novel biomarker signatures of dystrophinopathies will be indispensible for the swift evaluation of innovative therapeutic approaches, such as exon skipping, codon-read-through or stem cell therapy.

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“…In recent years, proteomics and metabolomics analysis have been progressively applied to offer innovative views to treat MG. Gomez et al indicate that transformations in cytoplasmic proteins are implicated in the pathogenesis of MG [ 17 ]. Serum proteomic and metabolomic analyses were performed with myasthenia gravis patients to explore the therapeutic effect of Qiangji Jianli Fang on MG [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated proteomics and metabolomics analysis reveals hubs protein and network alterations in myasthenia gravis

Tong

Zhang

et al. 2022

Aging

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Background: Thymoma-associated myasthenia gravis (TAMG) is a well-described subtype of Myasthenia gravis (MG). Nevertheless, the detailed proteins and bioprocess differentiating TAMG from TAMG (−) thymoma have remained unclear. Methods: The proteomics and metabolomics were carried out on serum samples from thymoma group ( n = 60, TNMG), TAMG (+) thymoma group ( n = 70, TAMG (+)), and TAMG (−) thymomas group ( n = 62, TAMG (−)), and controls ( n = 159). groups. Proteomics and metabolomics analyses, including weighted gene co-expression network analysis (WGCNA), was conducted to detect the hub proteins and metabolomics processes that could differentiate TAMG (+) from TAMG (−) thymomas. MetaboAnalyst was used to examine the integration of proteomic and metabolomic analysis to differentiate TAMG (+) from TAMG (−) thymomas. Results: The of module–trait correlation of WGCNA analysis identified KRT1, GSN, COL6A1, KRT10, FOLR2, KRT9, KRT2, TPI1, ARF3, LYZ, ADIPOQ, SEMA4B, IGKV1-27, MASP2, IGF2R was associated with TAMG (+) thymomas. In addition, organismal systems-immune system and metabolism-biosynthesis of other secondary metabolites were closely related to the mechanism of TAMG (+) pathogenesis. Conclusion: Our integrated proteomics and metabolomics analysis supply a systems-level view of proteome changes in TAMG (+), TAMG (−) thymomas and exposes disease-associated protein network alterations involved in.

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Proteomic analysis of rat tibialis anterior muscles at different stages of experimental autoimmune myasthenia gravis

Cited by 11 publications

References 27 publications

Plasma vitronectin is reduced in patients with myasthenia gravis: Diagnostic and pathophysiological potential

Plasma vitronectin is reduced in patients with myasthenia gravis: Diagnostic and pathophysiological potential

Mass Spectrometry-Based Identification of Muscle-Associated and Muscle-Derived Proteomic Biomarkers of Dystrophinopathies

Integrated proteomics and metabolomics analysis reveals hubs protein and network alterations in myasthenia gravis

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