Relationship between cerebrospinal fluid cytokines/chemokines and clinical impact of myelin oligodendrocyte glycoprotein antibody-associated disorders in children

Abstract

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has been increasingly reported in children at the first presentation of an acquired central nervous system (CNS) demyelinating disorder and can have a relapsing course. This study aimed to evaluate cerebrospinal fluid (CSF) cytokine/chemokine profiles in children with acute-phase inflammatory demyelinating disorders according to MOG-IgG positivity and/or recurrent relapses.

Methods: A total of 24 cytokines/chemokines were measured using multiplex immunoassay in the CSF of 85 children, who were divided into serum MOG-IgG positive (MOG-P, n = 28) [acute disseminated encephalomyelitis (n = 19), optic neuritis (n = 8), neuromyelitis optica spectrum disorder (n = 1)] group, MOG-negative (MOGN, n = 27) demyelinating disorder group, and control (n = 30) group.

Results: All four CSF B-cell related (APRIL, BAFF, BLC/CXCL13, and MIP-3β/CCL19), Treg-related (IL-10), and the majority of CSF Th17-related (IL-6, IL-17 A, IL-21, G-CSF/CSF-3, and GM-CSF) cytokines/chemokines were significantly elevated during the acute phase in the MOG-P group compared to the MOG-N group. The mean values of B-cell-related and Treg-related (IL-10) molecules, as well as the seropositivity rate for MOG-IgG, were significantly higher in the relapse group than in the non-relapse group. Furthermore, the levels of all B-cell- and Treg-related IL-10, along with two Th17-related cytokines (IL-6, and IL-17 A), were positively correlated with the MOG-IgG titers in children with MOGAD.

Conclusion: Children with MOG-IgG positivity exhibit a pronounced CNS inflammatory response characterized by elevated levels of humoral immunity-associated cytokines/chemokines, and selected Th17-related molecules. CSF cytokine/chemokine profiles may aid in predicting relapse, monitoring inflammation and disease activity, and identifying novel therapeutic targets in pediatric MOGAD.

Keywords: Cerebrospinal fluid; Chemokines; Child; Cytokines; Demyelinating diseases; Myelin oligodendrocyte glycoprotein; Recurrence.