Expression of CXCR 3 and its ligands CXCL 9, ‐10 and ‐11 in paediatric opsoclonus–myoclonus syndrome

Summary Opsoclonus–myoclonus syndrome ( OMS ) is a neuroinflammatory disorder associated with remote cancer. To understand more clearly the role of inflammatory mediators, the concentration of CXCR 3 ligands CXCL 10, CXCL9 and CXCL 11 was measured in 245 children with OMS and 81 paediatric controls using enzyme‐linked immunosorbent assay ( ELISA) , and CXCR 3 expression on CD 4 + T cells was measured by flow cytometry. Mean cerebrospinal fluid ( CSF ) CXCL 10 was 2·7‐fold higher in untreated OMS than controls. Intrathecal production was demonstrated by significantly different CXCL 10 CSF  : serum ratios. The dichotomized ‘high’ CSF CXCL 10 group had higher CSF leucocyte count ( P  = 0·0007) and B cell activating factor ( BAFF) and CXCL 13 concentrations ( P  < 0·0001). CSF CXCL 10 did not correlate with clinical severity or relapse using grouped data, although it did in some patients. Among seven types of immunotherapy, including rituximab or chemotherapy, only adrenocorticotrophic hormone ( ACTH) monotherapy showed reduced CSF CXCL 10, but prospective longitudinal studies of ACTH combination therapies indicated no reduction in CXCL 10 despite clinical improvement ( P  < 0·0001). CXCL 10 concentrations were 11‐fold higher in CSF and twofold higher in serum by multiplexed fluorescent bead‐based immunoassay than enzyme‐linked immunosorbent assay, but the two correlated ( r  = 0·7 and 0·83). In serum, no group differences for CXCL 9 or CXCL 11 were found. CXCR 3 expression on CD 4 + T cells was fivefold higher in those from CSF than blood, but was not increased in OMS or altered by conventional immunotherapy. These data suggest alternative roles for CXCL 10 in OMS . Over‐expression of CXCL 10 was not reduced by clinical immunotherapies as a whole, indicating the need for better therapeutic approaches.