Multiple Sclerosis is an inflammatory neurodegenerative disease with autoimmune components that exacerbate and potentially initiate the disease. Diagnosis is invasive, time-consuming, relatively expensive and extremely difficult. In fact no clear diagnostic test yet exist. A major concern is that MS symptoms are identical to the symptoms of numerous other neurologic diseases (OND) as well as some infectious diseases, thus making diagnosis particularly tricky. The disease occurs in different courses including relapsing/remitting and progressive forms. The etiologies of disease and progression are unclear. Autoimmune components define MS from OND and became better understood through the EAE mouse model. The central problem has been defining a reliable biomarker for pathogenic cells. We described a unique T cell subset, Th40 cells (CD4+CD40+ T cells) that are highly auto-aggressive. We compared Th40 levels in peripheral blood of patients with clinically isolated syndrome (CIS), relapsing/remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) disease to non- autoimmune controls. MS subjects demonstrate significantly increased percentages of Th40 cells. In reverse translation studies we confirmed the role of Th40 cells as disease causing in EAE. The role of CD40 is well established in MS. We are proposing that a screening platform for MS can be generated based on CD4 and CD40 co-staining. Using antibodies for those molecules we can show that CD4+CD40+ cells are significant in MS compared to non- autoimmune controls. Antibody staining is problematic requiring consistent compensations during detection. We created a series of peptides based on the CD154 (the major ligand for CD40) sequence. We determined that some of those peptides bind directly to CD40 and importantly when the antibodies are fluorescently tagged, the peptides discern CD40+ cells. From that data we propose that these peptides can be used to create a screening platform for the autoimmune component of MS. This technology would create not only a new test to distinguish MS from OND, and infectious disease but a new way to stain cells. Therefore the commercial opportunity is high for neurology and for staining product development. If successful this screening platform could distinguish MS. This product has high significance given the high possibility for misdiagnosing MS. Extension of the product may be a means to predict MS progression and to confirm disease modulating therapy efficacy.

R41AI129571

2017-08-01

2019-07-31