Dysregulation of the IL-23/IL-17 axis and myeloid factors in secondary progressive MS.

Objective: In the current exploratory study, we longitudinally measured immune parameters in the blood of individuals with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and investigated their relationship to disease duration and clinical and radiologic measures of CNS injury.

Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from subjects with RRMS, SPMS, and from healthy controls on a monthly basis over the course of 1 year. MRI and Expanded Disability Status Scale evaluations were performed serially. PBMCs were analyzed by enzyme-linked immunosorbent spot assay to enumerate myelin basic protein-specific interleukin (IL)-17- and interferon (IFN)-γ-producing cells. Plasma concentrations of proinflammatory factors were measured using customized Luminex panels.

Results: Frequencies of myelin basic protein-specific IL-17- and IFN-γ-producing PBMCs were higher in individuals with RRMS and SPMS compared to healthy controls. Patients with SPMS expressed elevated levels of IL-17-inducible chemokines that activate and recruit myeloid cells. In the cohort of patients with SPMS without inflammatory activity, upregulation of myeloid-related factors correlated directly with MRI T2 lesion burden and inversely with brain parenchymal tissue volume.

Conclusions: The results of this exploratory study raise the possibility that Th17 responses and IL-17-inducible myeloid factors are elevated during SPMS compared with RRMS, and correlate with lesion burden. Our data endorse further investigation of Th17- and myeloid-related factors as candidate therapeutic targets in SPMS.