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Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid
Published on: December 4, 2017
Cerebrospinal fluid metabolomic signatures in paediatric MOGAD and POMS
Piera De Gaspari1,2, Stefano Sartori1,3, Margherita Nosadini1,3
1Neuroimmunology group, Paediatric Research Institute "IRP Città della Speranza", Padova, Italy.
Insights
Metabolomic and lipidomic analyses of cerebrospinal fluid (CSF) can help differentiate Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) from paediatric-onset multiple sclerosis (POMS). These omic analyses offer a novel diagnostic approach for early identification of demyelinating disorders in children.
Area of Science:
- Neuroscience
- Biochemistry
- Pediatric Neurology
Background:
- Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and paediatric-onset multiple sclerosis (POMS) are acquired demyelinating syndromes (ADSs) with overlapping clinical and MRI features but distinct prognoses and management strategies.
- Accurate early diagnosis of POMS is crucial for limiting disability, while differentiating it from MOGAD is essential for appropriate patient management and counseling.
- Current diagnostic biomarkers, including CSF analysis and MRI, are not always definitive, especially at disease onset, highlighting the need for novel diagnostic approaches.
Purpose of the Study:
- To investigate the utility of cerebrospinal fluid (CSF) metabolomic and lipidomic profiling for differentiating MOGAD and POMS in children.
- To identify novel biomarkers for early and accurate diagnosis of pediatric demyelinating disorders.
Main Methods:
- High-sensitivity shotgun mass spectrometry was employed to analyze the CSF metabolome and lipidome.
- The study compared CSF profiles of children with MOGAD and POMS against a control group with non-demyelinating diseases.
- Analysis included 128 hydrophilic metabolites and 210 lipids, with statistical adjustments for multiple comparisons (FDR) and effect size evaluation.
Main Results:
- Distinct changes in CSF metabolic concentrations were observed between MOGAD and POMS, primarily involving energy metabolism pathways.
- Specific lipidomic alterations included the accumulation of plasmalogens, phosphatidylethanolamine (PE), and cholesterol esters in MOGAD.
- POMS exhibited higher signal intensities for very-long-chain PE and triglycerides (TG), though these findings require validation in larger cohorts.
Conclusions:
- CSF metabolomic and lipidomic profiling provides a valuable, fast, and reliable method for biomarker discovery in pediatric demyelinating neurological disorders.
- Broad-range omic analysis can serve as a complementary diagnostic tool to existing biomarkers for early disease identification.
- These findings support the potential of metabolomics and lipidomics in improving the differential diagnosis and management of MOGAD and POMS.
Introduction:
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and paediatric-onset multiple sclerosis (POMS) are acquired demyelinating syndromes (ADSs) that are increasingly recognised in paediatric care. They share clinical and magnetic resonance imaging (MRI) features, but they differ in prognosis and management, as POMS is a chronic inflammatory neurodegenerative disorder, whereas MOGAD is not. Early POMS diagnosis is essential to limit disability accumulation. Thus, early identification of these syndromes is key to their adequate management and family counselling and improving the outcome. Cerebrospinal fluid (CSF) biochemistry and cell count, oligoclonal band, IgG index, and serum MOG antibodies, together with brain and spine MRI, are the most valuable diagnostic biomarkers for differential diagnosis. However, it is not always possible to rely on these specific biomarkers to correctly identify these syndromes, especially at disease onset. In this perspective, metabolomic and lipidomic analyses have recently gained ground as a novel diagnostic approach.
Methods:
In the present study, high-sensitivity shotgun mass spectrometry was used to characterise the CSF metabolome and lipidome of children with MOGAD and POMS disorders compared with the CSF of children with non-demyelinating diseases used as controls.
Results:
The identification of 128 CSF hydrophilic metabolites and 210 lipids revealed characteristic changes in the relative metabolic concentrations in MOGAD compared with POMS, mainly related to the energy metabolism pathways. The lipidomic profile revealed the accumulation of the plasmalogens phosphatidylethanolamine (PE) and cholesterol esters as specific features of the lipid metabolic derangement. In this exploratory cohort, POMS showed higher very-long-chain PE and triglyceride (TG) signal intensities after false discovery rate (FDR) correction and effect size evaluation; however, these trends require confirmation in larger, independent cohorts.
Conclusion:
By exploring the CSF metabolomic profile, we demonstrated the usefulness of broad-range omic analysis as a fast and reliable method of biomarker discovery in children with demyelinating neurological disorders at the onset of the disease, which may be a valuable diagnostic complement to the existing biomarkers.
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