Profiling blood-based brain biomarkers and cytokines in experimental autoimmune encephalomyelitis model of multiple sclerosis using single molecule array technology

Experimental autoimmune encephalomyelitis (EAE) remains widely used pre-clinical animal model to study multiple sclerosis (MS). Blood-based cytokines and CNS biomarkers are increasingly used as predictors of neurodegeneration, disease activity and disability in MS. However, there exists variation in animal model characterization and disease course across animal strains/studies due to understudied confounding factors, limiting the utility of these biomarkers to predict disease activity in EAE. In this study, we investigated the profile of blood-based analytes including, cytokines (IL6, IL17, IL12p70, IL10, and TNFα) and neural markers (NFL and GFAP) in the plasma of relapsing-remitting (RR) (SJL) and chronic (B6) models of EAE during different phases (acute, chronic, and progressive) of disease course using ultrasensitive single molecule array technology (SIMoA, Quanterix), which can detect ultra-low levels of a wide range of analytes. NFL showed substantial increase during post-disease onset at peak, chronic and progressive phases in both RR SJL and chronic B6 models of EAE. The increase was markedly pronounced in chronic B6 model. The leakage of GFAP from CNS into periphery was also higher after disease onset in EAE, however, it was highest during acute phase in B6. Out of all cytokines, only IL10 showed consistently lower levels in both models of EAE along the disease duration. We report that NFL, GFAP, and IL10 may be more useful predictors of disease activity and neurological outcome in EAE, which would make them potential candidates for use as surrogate markers for preclinical testing of therapeutic interventions in MS.