Paediatric onset of multiple sclerosis: Analysis of chemokine and cytokine levels in the context of the early clinical course

Abstract

BackgroundInflammatory activity in children with paediatric onset multiple sclerosis (POMS) is higher than that in adults with MS. Chemokine/cytokine profiling in children may provide new insights into the disease pathogenesis and clinical course. The levels of chemokines/cytokines and their roles in POMS remain largely unknown. ObjectiveTo identify the possible utility of chemokines/cytokines in children with POMS, we analysed their levels at the time of disease diagnosis and in the context of subsequent clinical relapse. MethodsCC and CXC motif ligand chemokines (CCL2, CXCL8, CXCL10, and CXCL13), interleukin (IL)-4, IL-17A, interferon gamma and B cell-activating factor in the blood and cerebrospinal fluid (CSF) of 34 POMS patients and 20 age-related controls were measured using Luminex multiplex bead and enzyme-linked immunosorbent assay techniques. Nonparametric tests were used for statistical analyses. ResultsThe CSF levels of CXCL8 (p = 0.002), CXCL10 (p = 0.001), and CXCL13 (p<0.0001) were higher in POMS than in controls; CXCL10 and CXCL13 correlated with pleocytosis and oligoclonal bands. A subsequent clinical relapse occurred in 17/34 of the children; the median time from the diagnosis of POMS was 6 months (range, 2–64 months). The follow-up period of patients who did not experience a clinical relapse was significantly longer than the time to first relapse (p = 0.003). The initial CCL2 level was lower in relapsing than in non-relapsing patients (p = 0.063) and correlated negatively with the CSF/serum albumin ratio and positively with the time to relapse (p<0.04). ConclusionsElevated CSF levels of CXL10 and CXCL13 in children with POMS at the time of disease diagnosis reflect inflammatory activity and suggest the involvement of adaptive immunity; elevated CXCL8 levels further indicate the involvement of innate immunity. An initial low CSF level of CCL2 may be associated with an unfavourable early MS course.