BACKGROUND AND PURPOSE: Susceptibility to multiple sclerosis (MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. METHODS: This preliminary study utilized pre-symptomatic and post-symptomatic serum from a sample of 100 incident population-based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program. RESULTS: The mean intervals between first symptom onset and the collection of pre-symptomatic and post-symptomatic sera were -6.0 and +1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors. CONCLUSIONS: Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.
BACKGROUND AND PURPOSE: Susceptibility to multiple sclerosis (MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. METHODS: This preliminary study utilized pre-symptomatic and post-symptomatic serum from a sample of 100 incident population-based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program. RESULTS: The mean intervals between first symptom onset and the collection of pre-symptomatic and post-symptomatic sera were -6.0 and +1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors. CONCLUSIONS: Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.