Role of SLAMF Immunoregulatory Molecules in the MS Disease Processes
Friday, September 16, 2016 — Poster Session IV
- J Park
- R Masvekar
- P Kosa
- B Bielekova
In our unbiased proteomic analysis of cerebrospinal fluid (CSF) biomarkers we identified signaling lymphocyte activation molecules family (SLAMF) as significantly upregulated in multiple sclerosis (MS) patients in comparison to not only healthy controls (HC), but also patients with other types of CNS inflammation. Machine learning identified four SLAMF members as crucial components of the molecular MS diagnostic test we have developed and validated: CD48 (SLAMF2), LY9 (SLAMF3, CD229), CD84 (SLAMF5) and CD319 (SLAMF7). These immunoregulatory receptors interact with SLAM-associated protein mutated in X-linked lymphoproliferative disease, which is characterized by a fatal response to Epstein Barr Virus (EBV) infection. Intriguingly, EBV is a leading environmental MS susceptibility factor. Consequently, over-representation of SLAMF family members in the diagnostic classifier for MS represents a biological link between EBV infection and immunopathogenesis of MS, as SLAMF members regulate germinal center reactions, production of immunoglobulins, cytotoxicity, cell adhesion and immune cell survival. The goal of this project is to gain a mechanistic understanding of SLAMF molecules in MS disease processes.