Blood IgG antibodies as biomarkers for multiple sclerosis. There is a great unmet need for a sensitive and specific blood biomarker for early diagnosis of multiple sclerosis (MS), and for evaluating responses to therapeutics. In collaboration with Dr. Vollmer and Dr. Alvarez from the Department of Neurology (https://medschool.cuanschutz.edu/neurology/faculty), we are developing serum antibody-based ELISA assays for MS diagnosis and for monitoring patients’ response to therapies.
MS IgG antibodies as therapeutic targets for drug screening. We have demonstrated that MS serum antibodies produced complement-dependent cytotoxicity in neurons and brain tissues. We further showed that levels of MS serum cytotoxicity can be used to monitor patient response to disease-modifying therapies. In collaboration with Dr. LaBarbera of School of Pharmacy (https://pharmacy.cuanschutz.edu/about-us/profile/daniel-labarbera, we are screening drug libraries to targeting MS antibody induced neuronal cell death.
Phage-displayed random peptide libraries for identification of extracellular vesicles. We have identified high affinity peptides specific for Extracellular vesicles from patients with glioblastoma. As multiple PI with Dr. Graner (https://som.ucdenver.edu/Profiles/Faculty/Profile/6355), we are using random peptide approach screen and characterize EVs from patients with brain tumors, traumatic brain injuries, MS, and other CNS disorders for identification of EV biomarkers.
Kennedy, PGE, Graner, M., Li, X., Pointon, T., Dennison, K., Im, G., Curley, T., Tanimoto, K., Frank, L., Vollmer, T., Yu, X. Aberrant Immunoglobulin G glycosylation in Multiple Sclerosis. Journal of Neuroimmune Pharmacology. 2021. https://link.springer.com/article/10.1007/s11481-021-09996-1.
Graner M., Pointon T., Manton S., Green M., Dennison K., Davis M., Braiotta G., Craft J., Edwards T., Polonsky B., Fringuello A., Vollmer T., Yu X. Oligoclonal IgG Antibodies in Multiple Sclerosis Target Patient-Specific Peptides. 2020. PLOS ONE 15(2). https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0228883
Yu, X., Graner, M., Kennedy, PGE., Liu. Y., The Role of Antibodies in the Pathogenesis of Multiple Sclerosis. Frontiers in Neurology. 2020. 11: 533388. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606501/.
Wang, Z., Kennedy, PGE, Dupree, C., Wang, M, Lee, C., Pointon, T., Langford, TD, Graner, M., Yu, X. Antibodies from multiple sclerosis brain identified Epstein-Barr virus nuclear antigen 1 & 2 epitopes which are recognized by oligoclonal bands. Journal of neuroimmune pharmacology. 2021. https://pubmed.ncbi.nlm.nih.gov/32808238/
Beseler C, Vollmer T, Graner M, Yu X. The complex relationship between oligoclonal bands, lymphocytes in the cerebrospinal fluid, and immunoglobulin G antibodies in multiple sclerosis: Indication of serum contribution. 2017. PLOS ONE 12(10): e0186842. https://pubmed.ncbi.nlm.nih.gov/29059249/