Metabolomic Analysis of Membranous Glomerulonephritis: Identification of a Diagnostic Panel and Pathogenic Pathways

Taherkhani, Amir; Nafar, Mohsen; Oskouie, Afsaneh Arefi; Broumandnia, Nasrin; Parvin, Mahmoud; Mahmoudieh, Leila; Kalantari, Shiva

doi:10.1016/j.arcmed.2019.08.004

Cited by 16 publications

(12 citation statements)

References 40 publications

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“…Multi-omics techniques have been extensive applied to the biomarker discovery, diagnosis and prognosis, drug pharmacological and toxicity evaluation in a variety of diseases including ( Cisek et al, 2016 ; Yang, 2020 ; Joshi et al, 2021 ). Although a number of studies of systems biology have been performed on exploring the pathomechanisms of CKD through analyzing DNA, RNA, proteins, metabolites and their molecular and metabolic pathways, the metabolomics in MN is still in its infancy compared with other CKD ( Jiang et al, 2013 ; Cisek et al, 2016 ; Taherkhani et al, 2019 ).…”

Section: Systems Biology-based Mechanisms In Imnmentioning

confidence: 99%

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Miao

Zhang

et al. 2022

Front. Pharmacol.

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Membranous nephropathy (MN) is a renal-limited non-inflammatory autoimmune disease in the glomerulus, which is the second or third main cause of end-stage kidney diseases in patients with primary glomerulonephritis. Substantial achievements have increased our understanding of the aetiology and pathogenesis of murine and human MN. The identification of nephritogenic autoantibodies against neutral endopeptidase, phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by specific B cell-targeting monoclonal antibodies to inhibit antibody production and antibody-antigen immune complex deposition. Furthermore, additional antibody specificities for antigens have been discovered, but their pathogenic effects are uncertain. Although anti-PLA2R and anti-THSD7A antibodies as a diagnostic marker is widely used in MN patients, many questions including autoimmune response development, antigenic epitopes, and podocyte damage signalling pathways remain unresolved. This review describes the current available evidence regarding both established and novel molecular mechanisms based on systems biology approaches (gut microbiota, long non-coding RNAs, metabolite biomarkers and DNA methylation) in MN, with an emphasis on clinical findings. This review further summarizes the applications of traditional Chinese medicines such as Tripterygium wilfordii and Astragalus membranaceus for MN treatment. Lastly, this review considers how the identification of novel antibodies/antigens and unresolved questions and future challenges reveal the pathogenesis of MN.

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Section: Systems Biology-based Mechanisms In Imnmentioning

confidence: 99%

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Miao

Zhang

et al. 2022

Front. Pharmacol.

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“…In total, 509 and 411 proteins were identified in TMT1 and TMT2, respectively, and 249 proteins were identified in two technical replicates, of which urine alpha-1-antitrypsin (A1AT) and afamin (AFM) were oversecreted in patients with PMN. In addition, Taherkhani et al (53) analyzed the urinary metabolomes of 66 patients with MN, 31 healthy controls, and 72 disease controls by nuclear magnetic resonance (NMR) and GC-MS/MS. A set of seven metabolites (a-hydroxybutyric acid, 3,4-dihydroxymandelic acid, 5a-cholestanone, 2-hydroxyglutaric acid lactone, nicotinamide,epicoprostanol, and palmitic acid) was the best diagnostic predictor of MN.…”

Section: Mn-related Non-podocyte Autoantigen or Autoantibody Biomarke...mentioning

confidence: 99%

Novel Biomarkers in Membranous Nephropathy

Liu

Lin

et al. 2022

Front. Immunol.

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Membranous nephropathy (MN) is the main cause of adult nephrotic syndrome (NS). The pathogenesis of MN is complex and involves subepithelial immune complex deposition. Approximately one-third of patients with MN develop end-stage renal disease (ESRD). Timely diagnosis and reasonable intervention are the keys to improving prognosis. In recent years, with the development of high-throughput technologies, such as mass spectrometry (MS), microarray, and sequencing technologies, the discovery of biomarkers for MN has become an important area of research. In this review, we summarize the significant progress in biomarker identification. For example, a variety of podocyte target antigens and their autoantibodies have been reported. Phospholipase A2 receptor (PLA2R) is the most well-established target antigen in MN. PLA2R and its autoantibodies have clinical significance, with both diagnostic and therapeutic value for MN. In addition, a variety of new biomarkers, including proteins, metabolites, noncoding RNAs (ncRNAs), and immune cells, have recently been found. These MN-related biomarkers have great significance in the diagnosis, progression, prognosis, and treatment response of MN.

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“…Combining Nuclear Magnetic Resonance and Mass Spectrometry Techniques for Personalized Medicine: Where Do We Stand? Some studies apply both NMR and MS-based analytical strategies to clinical research to combine the respective biomarkers of interest, and include them in a common metabolic pathway analysis, as it was done to study the primary membranous glomerylonephritis and the subsequent nephrotic syndrome that it can cause in adults (Taherkhani et al, 2019). Others use NMR as a primary tool for open-profiling metabolomics, and then use subsequent LC-MS/MS to confirm the results obtained by NMR or to quantitatively target a subset of metabolites.…”

Section: Nuclear Magnetic Resonance and Mass Spectrometry Techniques As The Keystones Of Fluxomicsmentioning

confidence: 99%

Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives

Letertre

Giraudeau

Tullio

2021

Front. Mol. Biosci.

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Personalized medicine is probably the most promising area being developed in modern medicine. This approach attempts to optimize the therapies and the patient care based on the individual patient characteristics. Its success highly depends on the way the characterization of the disease and its evolution, the patient’s classification, its follow-up and the treatment could be optimized. Thus, personalized medicine must combine innovative tools to measure, integrate and model data. Towards this goal, clinical metabolomics appears as ideally suited to obtain relevant information. Indeed, the metabolomics signature brings crucial insight to stratify patients according to their responses to a pathology and/or a treatment, to provide prognostic and diagnostic biomarkers, and to improve therapeutic outcomes. However, the translation of metabolomics from laboratory studies to clinical practice remains a subsequent challenge. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are the two key platforms for the measurement of the metabolome. NMR has several advantages and features that are essential in clinical metabolomics. Indeed, NMR spectroscopy is inherently very robust, reproducible, unbiased, quantitative, informative at the structural molecular level, requires little sample preparation and reduced data processing. NMR is also well adapted to the measurement of large cohorts, to multi-sites and to longitudinal studies. This review focus on the potential of NMR in the context of clinical metabolomics and personalized medicine. Starting with the current status of NMR-based metabolomics at the clinical level and highlighting its strengths, weaknesses and challenges, this article also explores how, far from the initial “opposition” or “competition”, NMR and MS have been integrated and have demonstrated a great complementarity, in terms of sample classification and biomarker identification. Finally, a perspective discussion provides insight into the current methodological developments that could significantly raise NMR as a more resolutive, sensitive and accessible tool for clinical applications and point-of-care diagnosis. Thanks to these advances, NMR has a strong potential to join the other analytical tools currently used in clinical settings.

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Metabolomic Analysis of Membranous Glomerulonephritis: Identification of a Diagnostic Panel and Pathogenic Pathways

Cited by 16 publications

References 40 publications

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Novel Biomarkers in Membranous Nephropathy

Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives

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