4.7 Article

Proteomics Urine Analysis of Pregnant Women Suffering from Multiple Sclerosis

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 14, Issue 5, Pages 2065-2073

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/pr501162w

Keywords

pregnancy; third trimester; postpartum period; mass spectrometry; multiple sclerosis; urine

Funding

  1. EC Seventh Framework Programme of Marie Curie Initial Training Network - The United Europeans for the Development of Pharmacogenomics in Multiple Sclerosis (UEPHA-MS) [PITN-GA-2008212877]
  2. Netherlands Multiple Sclerosis Research Foundation
  3. ErasMS
  4. Netherlands Organization for Scientific Research (ZON-MW)
  5. Hersenstichting Nederland

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Multiple sclerosis (MScl) frequently is remitted during the third trimester of pregnancy but exacerbated in the first postpartum period. In this context, we investigated protein identification; its abundance, and its change in urine related to these two periods. Using mass spectrometry (LTQ Orbitrap), we identified 160 tryptic peptides (related to 402 proteins) in urine from 31 MScl and 8 control at these two periods. Pregnancy-related peptides were significantly elevated (p < 0.01) in MScl patients compared with controls (Analysis 1: 531 peptides in MScl and 36 peptides in controls higher abundant in the third trimester compared to postpartum). When comparing the longitudinal differences (Analysis 2), we identified 43 (related to 35 proteins) MScl disease-associated peptides (p < 0.01) with increased or decreased difference ratio in MScl compared with controls. The most discriminating peptides identified were trefoil factor 3 and lysosomal-associated membrane protein 2. Both proteins have a role in the innate immune system. Three proteins with a significant decreased ratio were plasma glutamate carboxypeptidase, Ig mu chain C region, and osteoclast associated immune like receptor. Our results indicate that the protein expression pattern in urine of MScl patients contains information about remote CNS and brain disease processes.

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