Exploring the human tear fluid: discovery of new biomarkers in multiple sclerosis.
OBJECTIVE
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.


METHODS
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
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.
Translational Biomarker Group, Department of Human Protein Sciences, Medical University Center, Geneva, Switzerland.
Cindy
C
Salvisberg
Nadja
N
Tajouri
Alexandre
A
Hainard
Pierre R
PR
Burkhard
Patrice H
PH
Lalive
Natacha
N
Turck
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism; D040901:Proteomics; D013666:Tears / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers; D005136:Eye Proteins; C042434:tear proteins
Biomarkers; Isobaric labeling; Multiple sclerosis; Tears