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Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, due especially to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in paediatric neuroinflammation, we immunophenotyped cerebrospinal fluid (CSF) and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurological disorders (NIND), 312 with opsoclonus-myoclonus (OMS) and 23 with other inflammatory neurological disorders (OIND). In NIND, the negative correlation between CSF γδ T cell frequency and patient age was striking: median frequency of 27% in infants and 3·3% in teens. Interindividual variations were largest in the youngest. There was no gender effect. In all OMS, after correcting for age, only a small effect of OMS severity remained. Measurement of markers for γδ T cell activation [human leucocyte antigen D-related (HLA-DR)], maturation (CD45RA, CD45RO) or intracellular cytokine staining [interleukin (IL)-4, interferon (IFN)-γ] failed to discriminate OMS and NIND groups. Of seven OMS immunotherapies/combinations, none altered the frequency of total CSF γδ T cells or subsets significantly. In OIND, the CSF γδ T cell frequency was < 10% for single samples of other paraneoplastic disorders [anti-neuronal nuclear antibody (ANNA)-1, PCA-1, teratoma-associated syndrome], cerebellar ataxia (post-infectious, ataxia-telangiectasia), acute disseminated encephalomyelitis, neuroborreliosis and encephalitis. This study provides new insights into CSF γδ T cells in the paediatric population. Although their role in CSF remains elusive, the negative age correlation, resistance to immunotherapy and our age cut-off references for NIND are important findings for the design of future paediatric studies., (© 2018 British Society for Immunology.)

Objective: To assess the role of microglia and macrophages in neuroinflammatory disorders in children via biomarkers, and establish control reference ranges., Methods: In an IRB-approved case-control study of 98 children, the concentrations of CSF/serum CHI3L1, sCD14, and sCD163 were measured by ELISA. Groups were controls (non-inflammatory neurological disorders, NIND, n=37), opsoclonus-myoclonus syndrome (OMS, n=37), and other inflammatory neurological disorders (OIND, n=24)., Results: In control CSF, median concentrations (ng/ml) were 25 (IQR 16,41) for CHI3L1 and 42 (26,160) for sCD14; in serum, 16 (12,22) for CHI3L1, and 431 (270,957) for sCD163. The median CSF concentration of CHI3L1 in OIND was significantly higher than controls (2.9-fold, P<0.0001) and OMS (1.6-fold higher than controls, NS). The CSF sCD14 concentration was 1.9-fold higher in OIND (P=0.008) and 1.4-fold higher in OMS than controls. sCD163, below detection limits in CSF, was not significantly increased in OIND or OMS sera., Conclusions: CSF CHI3L1 and sCD14 elevations hold promise as immunomarkers in pediatric OIND, especially in high-expression individuals. These results provide evidence of innate immune system involvement in several pediatric neuroinflammatory disorders. Pediatric control data on CSF microglia/macrophage activation markers are hereby available for other investigators., (Copyright © 2017 Elsevier B.V. All rights reserved.)