Metabolomics profile of MS

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frodo
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Metabolomics profile of MS

Post by frodo »

Several viral infections mimic MS. Before immune supresion or modulation is important to be sure that there is no infection in the CNS or things could get worse. This include viral and bacterial infections, like lyme disease.

Probably the best we have is MRS metabolomics. This recent article explains how MS can be sepparate from its mimics.

https://journals.plos.org/plosntds/arti ... td.0007045

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Discussion

NMR metabolomics distinguished infectious and inflammatory disorders using laboratory-confirmed samples of 5 disorders using 2 approaches to normalization of the data, and 2 unsupervised cluster analytical approaches. CART decision analysis easily differentiated bacterial (Lyme), fungal (Histoplasma) and viral (WNV) causes of encephalomyelitis from controls.

Decision analysis also differentiated rabies and the prodromal form of MS from controls, while separation by cluster analyses was incomplete between MS and controls. Notably, the greatest source of variation in metabolomics data found by PCA was the presence or absence of an infectious pathogen. If replicated, this finding is of paramount clinical impact because treatments for infections require almost polar opposite therapeutics than those for autoimmune diseases.

There was also substantial agreement in the identification of influential metabolites between different approaches to data normalization and reduction and predictive approaches, including CART and random forest analysis. Metabolites driving separation in PCA (pyruvate, glutamate, quinolinate, 2-oxoglutarate, carnitine, and glycine) potentially suggest alterations in energy metabolism, excitotoxicity and antioxidant response. Patterns of these metabolites were not uniform. Rather, overlapping as well as distinguishing metabolic features were seen, highlighting the potential utility of measuring a suite of metabolites rather than searching for individual metabolic biomarkers for diseases, which may not exist. Overlap of profiles makes strong clinical sense given that EM syndromes overlap in signs and symptoms. The overlap also supports a clinical rationale for syndromic metabolic therapies across a range of infectious or autoimmune causes of EM. Distinguishing features provide promise of rapid, relatively specific diagnoses that enable prompt pathogen or process-directed therapies.

[...]

All forms of encephalitis are treated empirically upon hospitalization, so early diagnostic samples such as those analyzed here may reflect early empirical therapies that often overlap (e.g., rehydration, provision of glucose, use of antibacterials, sedation) but may also differ between diseases. Our choice of rabies samples centered on the fourth day of hospitalization was intended to minimize effects of dehydration and malnutrition, but may have biased rabies samples toward normality. Finally, differences in some metabolites should be interpreted with caution, since low concentrations in some specimens precluded exact quantification (carnitine and glycine), which may have artificially led to statistical differences. Other metabolites (glutamine and pyroglutamate) are potentially affected by protein removal [45], although this has not been shown in CSF.

This study provides justification for further analysis of samples from these and other causes of encephalomyelitis. Several prominent and as of yet unidentified peaks observed in the spectra of some patients may indicate the presence of important metabolites involved in disease pathogenesis that have not yet been elucidated. While further studies with larger sample sizes will be needed to determine the clinical utility of NMR in the diagnosis of EM, NMR or other ‘omics technologies may in the future serve as a rapid initial screening test that would allow medical practitioners to initiate treatment with antivirals or biological immune modifiers, while patient samples can then be triaged to appropriate reference laboratories for confirmation without delaying treatment. Rabies and many arbovirus reference laboratories require specialized containment facilities, immunization of laboratory workers, and highly trained personnel who perform subjective assays such as immunofluorescence. Reference laboratories for rabies, arboviruses, bacteria and fungi are often dispersed geographically, leading to substantial requirements in volume, delay, and cost for diagnosis of encephalomyelitis when all are considered. NMR and MS instruments, on the other hand, exist at most research universities, i.e. at a state or provincial rather than national level. NMR analytical procedures are easily standardized and permit detection of multiple diseases using a single experiment, as illustrated here. NMR spectra can be transmitted electronically for analysis, which can be automated [46]. Decision analytical approaches such as CART and RF offer diagnostic flow charts that are easily implemented once validated, with quantifiable diagnostic probabilities. Considering current challenges, its relative ease of use makes NMR metabolomics of CSF a potentially important tool for emergent diseases and distinguishing between autoimmune and infectious EM.
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Similar research among IIDDs

Post by frodo »

Immune Cell Profiling of the Cerebrospinal Fluid Provides Pathogenetic Insights into Inflammatory Neuropathies

https://www.frontiersin.org/articles/10 ... 5/abstract

Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies.

Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63).

Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8 T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies.

Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies.
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