An approach for the analysis of axonal neuroinflammation by measuring dual biomarkers of oligodendrocytes and inflammatory cytokine in human plasma.

The myelin sheath surrounding axons is vulnerable to mechanical stresses after head injuries, as well as autoimmune attacks and degeneration in neurological disorders. Unfortunately, there is currently no effective method to assess these axonal conditions in individual patients. We have developed a sandwich immunoassay detecting dual signals of myelin oligodendrocyte glycoprotein (MOG) and interleukin 1B (IL1B) in human plasma ([IL1B on MOG]). While IL1B is one of common inflammation markers, its lack of tissue specificity is addressed by identifying IL1B on extracellular vesicles from oligodendrocytes isolated using anti-MOG, suggesting inflammation around axons. In 77 control subjects, plasma levels of [IL1B on MOG] did not increase more than 2 fold from baseline. During the sports season, 14% (151 football players) and 22% (18 rugby players) exhibited a substantial 2-17 fold increase, despite the absence of traumatic brain injuries. This elevation demonstrated a non-random pattern, with some individuals gradually rising towards the season's end, followed by a decline. [IL1B on MOG] levels also correlated with the clinical course of a post-concussion syndrome case. These data indicate that [IL1B on MOG] blood test is a potential marker for assessing mild axonal neuroinflammation.