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The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study

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  • Helle H Nielsen
  • Hans C Beck
  • Lars P Kristensen
  • Mark Burton
  • Tunde Csepany
  • Magdolna Simo
  • Peter Dioszeghy
  • Tobias Sejbaek
  • Manuela Grebing
  • Niels H H Heegaard
  • Zsolt Illes

Abstract

Objectives: Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO), NMO spectrum disorders (NMO-SD) and multiple sclerosis (MS). Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS. Methods: The proteins in urine samples from anti-aquaporin 4 (AQP4) seropositive NMO/NMO-SD patients (n = 32), patients with MS (n = 46) and healthy subjects (HS, n = 31) were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig) in the urine were validated by nephelometry in an independent cohort (n = 9–10 pr. groups). Results: The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002). Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD. Conclusion: The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS.

Suggested Citation

  • Helle H Nielsen & Hans C Beck & Lars P Kristensen & Mark Burton & Tunde Csepany & Magdolna Simo & Peter Dioszeghy & Tobias Sejbaek & Manuela Grebing & Niels H H Heegaard & Zsolt Illes, 2015. "The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study," PLOS ONE, Public Library of Science, vol. 10(10), pages 1-15, October.
    • Handle: RePEc:plo:pone00:0139659
    DOI: 10.1371/journal.pone.0139659
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