Judith N Wagner1, S Weis2, C Kubasta3, J Panholzer4, T J von Oertzen4. 1. Department of Neurology 1, Kepler University Hospital, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020, Linz, Austria. Judith.Wagner@kepleruniklinikum.at. 2. Department of Neuropathology, Kepler University Hospital, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020, Linz, Austria. 3. Department of Clinical Pathology, Kepler University Hospital, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020, Linz, Austria. 4. Department of Neurology 1, Kepler University Hospital, Johannes Kepler University Linz, Wagner-Jauregg-Weg 15, 4020, Linz, Austria.
Abstract
BACKGROUND: The C-X-C motif chemokine ligand 13 (CXCL13) and its receptor CXCR5 play an important role in the homing of B-lymphocytes. As a biomarker in the cerebrospinal fluid (CSF), CXCL13 has increasingly been used for the diagnosis of neuroborreliosis (NB). We evaluated the diagnostic and prognostic potential of CXCL13 for NB and other neuroinflammatory diseases in an unselected cohort, paying attention to those patients particularly who might benefit from newly emerging CXCL13-directed therapies. METHODS: We report the CSF CXCL13 concentrations and other relevant baseline characteristics for an unselected cohort of 459 patients. We compare different diagnostic groups and analyse the sensitivity and specificity of CSF CXCL13 as a marker of NB. The course of the CXCL13 concentrations is reported in a subgroup of 19 patients. RESULTS: We confirm the high diagnostic yield of CXCL13 for NB in this unselected cohort. The optimal cut-off for the reliable diagnosis of NB was 93.83 pg/ml, resulting in a sensitivity and specificity of 95 and 97%, respectively (positive predictive value 55.9%, negative predictive value 99.8%), surpassing the sensitivity of both serological testing and PCR. CSF CXCL13 concentration showed a swift response to therapy. Non-NB patients with high CSF CXCL13 concentrations suffered from meningeosis neoplastica or infectious encephalitis. CONCLUSIONS: CXCL13 is a valuable tool for the diagnosis and assessment of therapeutic response in NB. Furthermore, our data point towards an emerging role of CXCL13 in the diagnosis and prognosis of viral encephalitis and meningeosis neoplastica. These results are of particular interest in the light of recently developed approaches to CXCL13-directed therapeutic interventions.
BACKGROUND: The C-X-C motif chemokine ligand 13 (CXCL13) and its receptor CXCR5 play an important role in the homing of B-lymphocytes. As a biomarker in the cerebrospinal fluid (CSF), CXCL13 has increasingly been used for the diagnosis of neuroborreliosis (NB). We evaluated the diagnostic and prognostic potential of CXCL13 for NB and other neuroinflammatory diseases in an unselected cohort, paying attention to those patients particularly who might benefit from newly emerging CXCL13-directed therapies. METHODS: We report the CSF CXCL13 concentrations and other relevant baseline characteristics for an unselected cohort of 459 patients. We compare different diagnostic groups and analyse the sensitivity and specificity of CSF CXCL13 as a marker of NB. The course of the CXCL13 concentrations is reported in a subgroup of 19 patients. RESULTS: We confirm the high diagnostic yield of CXCL13 for NB in this unselected cohort. The optimal cut-off for the reliable diagnosis of NB was 93.83 pg/ml, resulting in a sensitivity and specificity of 95 and 97%, respectively (positive predictive value 55.9%, negative predictive value 99.8%), surpassing the sensitivity of both serological testing and PCR. CSF CXCL13 concentration showed a swift response to therapy. Non-NBpatients with high CSF CXCL13 concentrations suffered from meningeosis neoplastica or infectious encephalitis. CONCLUSIONS:CXCL13 is a valuable tool for the diagnosis and assessment of therapeutic response in NB. Furthermore, our data point towards an emerging role of CXCL13 in the diagnosis and prognosis of viral encephalitis and meningeosis neoplastica. These results are of particular interest in the light of recently developed approaches to CXCL13-directed therapeutic interventions.
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