Exploring the human tear fluid: Discovery of new biomarkers in multiple sclerosis

Authors

  • Cindy Salvisberg,

    1. Translational Biomarker Group, Department of Human Protein Sciences, Medical University Center, Geneva, Switzerland
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  • Nadja Tajouri,

    1. Division of Ophthalmology Neuchâtel Hospital, Department of Medicine, Switzerland
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  • Alexandre Hainard,

    1. Proteomics Core Facility, Medical University Center, Geneva, Switzerland
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  • Pierre R. Burkhard,

    1. Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Switzerland
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  • Patrice H. Lalive,

    1. Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Switzerland
    2. Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland
    3. Departments of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • Natacha Turck

    Corresponding author
    1. Translational Biomarker Group, Department of Human Protein Sciences, Medical University Center, Geneva, Switzerland
    • Correspondence: Dr. Natacha Turck, Translational Biomarker Group (TBG)/ Department of Human Protein Sciences, University Medical Centre (CMU), University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland

      E-mail: natacha.turck@unige.ch

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Abstract

Purpose

Multiple sclerosis is the first cause of progressive neurological disability among young adults living in Western countries. Its diagnosis is mostly based on clinical evaluation, neuroimaging, and in some cases cerebrospinal fluid (CSF) analysis, but no definitive diagnostic test exists. We proposed here that the exploration of tears from multiple sclerosis patients could lead to the discovery of new biomarkers.

Experimental design

Thirty multiple sclerosis patients (20% men) recruited to the Geneva University Hospitals were included in our study (mean age ± SD [years]: 42.4 ± 15.9). Twenty-five control patients (32% men) were also enrolled (mean age ± SD [years]: 42.7±15.1). Tears, CSF or blood was collected for each patient. Three independent quantitative (tandem mass tag) experiments were carried out between tears from multiple sclerosis and control patients. Protein verification was performed by Western blot on tears and CSF and by ELISA on serum samples.

Results

Combined proteomics analyses provided 185 identified tear proteins. Among the differential proteins, alpha-1 antichymotrypsin was the only one to be significantly increased in the three experiments with similar ratios (ratios 1.6 to 2.5, p < 0.05). Its tear, CSF and serum elevation were further confirmed by Western blot and ELISA, respectively.

Conclusions and clinical relevance

This study supports the concept that modifications of the tear proteome can reflect biological abnormalities associated with multiple sclerosis and perhaps other inflammatory conditions affecting the CNS. In addition, alpha-1 antichymotrypsin elevation in tear fluid emerges as a promising biomarker for the diagnosis of multiple sclerosis.

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