Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease

The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard...

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Հիմնական հեղինակներ: Jurynczyk, M, Probert, F, Yeo, T, Tackley, G, Claridge, T, Cavey, A, Woodhall, M, Arora, S, Winkler, T, Schiffer, E, Vincent, A, DeLuca, G, Sibson, N, Leite, M, Waters, P, Anthony, D, Palace, J
Ձևաչափ: Journal article
Հրապարակվել է: BioMed Central 2017
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author Jurynczyk, M
Probert, F
Yeo, T
Tackley, G
Claridge, T
Cavey, A
Woodhall, M
Arora, S
Winkler, T
Schiffer, E
Vincent, A
DeLuca, G
Sibson, N
Leite, M
Waters, P
Anthony, D
Palace, J
author_facet Jurynczyk, M
Probert, F
Yeo, T
Tackley, G
Claridge, T
Cavey, A
Woodhall, M
Arora, S
Winkler, T
Schiffer, E
Vincent, A
DeLuca, G
Sibson, N
Leite, M
Waters, P
Anthony, D
Palace, J
author_sort Jurynczyk, M
collection OXFORD
description The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these conditions are indeed different at a molecular level. The metabolites identified provide a molecular signature of each condition which is independent of antibody titre and EDSS, with potential use for disease monitoring and diagnosis.
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spelling oxford-uuid:c5d9f374-fd61-4937-a6f8-c32caa4b5c042022-03-27T06:34:07ZMetabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c5d9f374-fd61-4937-a6f8-c32caa4b5c04Symplectic Elements at OxfordBioMed Central2017Jurynczyk, MProbert, FYeo, TTackley, GClaridge, TCavey, AWoodhall, MArora, SWinkler, TSchiffer, EVincent, ADeLuca, GSibson, NLeite, MWaters, PAnthony, DPalace, JThe overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these conditions are indeed different at a molecular level. The metabolites identified provide a molecular signature of each condition which is independent of antibody titre and EDSS, with potential use for disease monitoring and diagnosis.
spellingShingle Jurynczyk, M
Probert, F
Yeo, T
Tackley, G
Claridge, T
Cavey, A
Woodhall, M
Arora, S
Winkler, T
Schiffer, E
Vincent, A
DeLuca, G
Sibson, N
Leite, M
Waters, P
Anthony, D
Palace, J
Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease
title Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease
title_full Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease
title_fullStr Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease
title_full_unstemmed Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease
title_short Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease
title_sort metabolomics reveals distinct antibody independent molecular signatures of ms aqp4 antibody and mog antibody disease
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