Cholesterol level correlate with disability score in patients with relapsing-remitting form of multiple sclerosis

Ďurfinová, Monika; Procházková, L; Petrleničová, D.; Bystrická, Zuzana; Orešanská, Katarína; Kuračka, L; Líška, Branislav

doi:10.1016/j.neulet.2018.10.030

Cited by 24 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Serum metabolites are attractive candidate biomarkers in MS, and have already been shown to have diagnostic (22,23,60) and prognostic (27,61,62) potential. Furthermore, they are relatively inexpensive to measure, and a blood-draw is less invasive and time-consuming than a lumbar puncture or MRI scan.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of models have been based on clinical information, but ML-generated serum lipid signatures have also successfully been used to identify (22) and stratify (23) MS patients. Circulating lipids are dysregulated in MS, and have been associated with disease progression (24)(25)(26)(27)(28). Indeed, circulating lipids can profoundly influence immune cell behavior (29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ

et al. 2020

View full text Add to dashboard Cite

Background: Neutralizing anti-drug antibodies (ADA) can greatly reduce the efficacy of biopharmaceuticals used to treat patients with multiple sclerosis (MS). However, the biological factors pre-disposing an individual to develop ADA are poorly characterized. Thus, there is an unmet clinical need for biomarkers to predict the development of immunogenicity, and subsequent treatment failure. Up to 35% of MS patients treated with beta interferons (IFNβ) develop ADA. Here we use machine learning to predict immunogenicity against IFNβ utilizing serum metabolomics data. Methods: Serum samples were collected from 89 MS patients as part of the ABIRISK consortium-a multi-center prospective study of ADA development. Metabolites and ADA were quantified prior to and after IFNβ treatment. Thirty patients became ADA positive during the first year of treatment (ADA+). We tested the efficacy of six binary classification models using 10-fold cross validation; k-nearest neighbors, decision tree, random forest, support vector machine and lasso (Least Absolute Shrinkage and Selection Operator) logistic regression with and without interactions. Results: We were able to predict future immunogenicity from baseline metabolomics data. Lasso logistic regression with/without interactions and support vector machines were the most successful at identifying ADA+ or ADA-cases, respectively. Furthermore, patients who become ADA+ had a distinct metabolic response to IFNβ in the first 3 months, with 29 differentially regulated metabolites. Machine learning algorithms could also predict ADA status based on metabolite concentrations at 3 months. Lasso logistic regressions had the greatest proportion of correct classifications [F1 score (accuracy measure) = 0.808, specificity = 0.913]. Waddington et al. Using Metabolomics to Predict Immunogenicity Finally, we hypothesized that serum lipids could contribute to ADA development by altering immune-cell lipid rafts. This was supported by experimental evidence demonstrating that, prior to IFNβ exposure, lipid raft-associated lipids were differentially expressed between MS patients who became ADA+ or remained ADA-. Conclusion: Serum metabolites are a promising biomarker for prediction of ADA development in MS patients treated with IFNβ, and could provide novel insight into mechanisms of immunogenicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A large-scale observational research found that higher TC level was linked to worsening disability in those suffering from multiple sclerosis (MS) (12). There were also a positive association between TC levels and disability scores in patients with relapsing-remitting form of MS (13). Another research suggested that high TG level increases the probability of recurrence of MS (14).…”

Section: Introductionmentioning

confidence: 99%

Triglyceride Level Is an Independent Risk Factor in First-Attacked Neuromyelitis Optica Spectrum Disorders Patients

Wen

Duan

et al. 2019

Front. Neurol.

View full text Add to dashboard Cite

Objective: To investigate prospective associations between triglyceride (TG) level and prognosis of first-attacked patients with neuromyelitis optica spectrum disorders (NMOSD).Methods: This retrospective study included 196 patients newly diagnosed with NMOSD from June 2014 to December 2018. Data of clinical parameters, including age of onset, sex, BMI, blood lipid levels, anti-aquaporin-4 status, serum glucose level, therapy regimens, comorbidities, initial Expanded Disability Status Scale (EDSS), relapses, and outcomes were collected. We used logistic regression models to examine the associations among relevant clinical factors and outcomes, and statistical analyses were performed using the SPSS 23.0 software.Results: Compared with the high TG group, residual EDSS was relatively lower in the normal TG group (median 1.0 vs. 2.0, P = 0.002). In the univariate analysis, TG level was positively correlated with outcomes (OR 1.75, 95% CI 1.18–2.60, P = 0.005) and relapses (OR 1.57, 95% CI 1.07–2.31, P = 0.02). Our stratified analysis suggested that patients with normal BMI (OR 4.90, 95% CI 2.10–11.44, P = 0.001) were closely correlated with poor recovery owing to increased TG level. In the multivariate analysis, a statistically significant association still existed between TG level and outcomes (OR 3.44, 95% CI 1.02–11.64; P = 0.040) after adjusting for various variables.Conclusions: In first-attacked NMOSD patients, TG level was positively associated with poor recovery. Early monitoring and treatment of elevated TG level in NMOSD patients are important.

show abstract

“…Evidence supports a role for lipid metabolism (including changes in cholesterol, oxysterols, sphingolipids and fatty acids) not only in MS pathogenesis, but also as biomarkers of disease activity and progression and as treatment targets (8)(9)(10)(11)(12)(13)(14). One hypothesis is that abnormal lipid-mediated signaling in immune cells could contribute to MS pathogenesis (15).…”

Section: Introductionmentioning

confidence: 99%

Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?

et al. 2021

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic neurological disease driven by autoimmune, inflammatory and neurodegenerative processes leading to neuronal demyelination and subsequent degeneration. Systemic lipid metabolism is disturbed in people with MS, and lipid metabolic pathways are crucial to the protective process of remyelination. The lipid-activated transcription factors liver X receptors (LXRs) are important integrators of lipid metabolism and immunity. Consequently, there is a strong interest in targeting these receptors in a number of metabolic and inflammatory diseases, including MS. We have reviewed the evidence for involvement of LXR-driven lipid metabolism in the dysfunction of peripheral and brain-resident immune cells in MS, focusing on human studies, both the relapsing remitting and progressive phases of the disease are discussed. Finally, we discuss the therapeutic potential of modulating the activity of these receptors with existing pharmacological agents and highlight important areas of future research.

show abstract

Cholesterol level correlate with disability score in patients with relapsing-remitting form of multiple sclerosis

Cited by 24 publications

References 30 publications

Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ

Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ

Triglyceride Level Is an Independent Risk Factor in First-Attacked Neuromyelitis Optica Spectrum Disorders Patients

Disrupted Lipid Metabolism in Multiple Sclerosis: A Role for Liver X Receptors?

Contact Info

Product

Resources

About