Gray matter is targeted in first-attack multiple sclerosis

Steven E Schutzer, Thomas E Angel, Tao Liu, Athena A Schepmoes, Fang Xie, Jonas Bergquist, László Vécsei, Denes Zadori, David G Camp 2nd, Bart K Holland, Richard D Smith, Patricia K Coyle, Steven E Schutzer, Thomas E Angel, Tao Liu, Athena A Schepmoes, Fang Xie, Jonas Bergquist, László Vécsei, Denes Zadori, David G Camp 2nd, Bart K Holland, Richard D Smith, Patricia K Coyle

Abstract

The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. In-depth off-line 2D-LC- MS/MS analysis…
Figure 1. In-depth off-line 2D-LC-MS/MS analysis of the CSF proteome of a pooled sample composed of CSF from all MS patients resulted in the identification of 2820 proteins, and the comparison to previous results obtained from analyses of healthy normals and other neurologic disease (OND) .
Figure 2. Label-free quantification of CSF proteins…
Figure 2. Label-free quantification of CSF proteins identified in patient and control samples.
A) Following the 1D LC-MS analysis of immunodepleted CSF samples we identified peptides referable to 86 proteins that show significant difference in abundance by ANOVA (p-value

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Source: PubMed

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