Cytokines and chemokines in cerebrospinal fluid in relation to diagnosis, clinical presentation and recovery in children being evaluated for Lyme neuroborreliosis

In Lyme neuroborrelios (LNB), the immune response has been in focus, but the association between different cytokines/chemokines and clinical manifestations in LNB patients has not been fully investigated. The aim of this study was to evaluate a large number of cytokines and chemokines in cerebrospinal fluid (CSF) in relation to diagnosis, clinical presentation and recovery in children being evaluated for LNB. Materials and methods: Pediatric patients (n = 105) were recruited at seven Swedish pediatric departments during 2010-14. Serum and CSF samples were drawn on admission, before start of antibiotic treatment. Patients diagnosed as Definite LNB or Possible LNB were categorized as LNBtot patients, all LNBtot patients presented with pleocytosis in CSF. Patients diagnosed as Non-LNB or Other diagnosis were categorized as Controls(tot), all controls(tot) presented without pleocytosis in CSF. Multiplex bead array (Luminex) kits were used for analyses of 41 different cytokines/chemokines in CSF (Millipore). Results: Twenty-eight cytokines/chemokines were detectable in CSF and the levels of 26 of these mediators were significantly higher in LNBtot patients than in Controls(tot). In a discriminant analysis, a combination of four cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) were shown to independently separate relevant patient groups. Furthermore, an IL-10/CXCL1 ratio was created and shown to have an improved diagnostic performance in distinguishing LNBtot vs Non-LNB patients, as compared to CXCL13 in CSF. No immune mediator differed significantly, when comparing LNBtot patients with different clinical presentation on admission or when comparing patients with or without recovery within 2 months of admission. Conclusion: A discriminant analysis was shown to be useful to distinguish the independently most important cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) in CSF, in order to discriminate LNBtot patients from Non-LNB patients. An IL-10/CXCL1 ratio was shown to have a promising diagnostic profile with a better performance than the chemokine CXCL13 in CSF. However, further evaluation is required to address future possible usefulness of these cytokines and chemokines in laboratory diagnostics in LNB, including control groups with neuro-inflammation. No significant associations were found between CSF immune mediator levels and clinical presentation or recovery in pediatric LNB patients.Funding Agencies|Regional Research Council Uppsala-Orebro [RFR-226161, RFR-462701]; Center for Clinical Research Dalarna - Uppsala University [CKFUU-105141, CKFUU-374651, CKFUU-566761]; Swedish Society of Medicine [SLS-498901, SLS-93191]; EU Interreg V A project ScandTick Innovation; Division of Clinical Microbiology, Region Jonkoping County., Sweden