The chemokine CXCL 13 in acute neuroborreliosis

Objective Recent studies have suggested an important role of the B cell chemoattractant CXCL13 in acute neuroborreliosis (NB). Our aim was to confirm the diagnostic role of CXCL13 and to evaluate its relevance as a therapy response and disease activity marker in NB. Methods CXCL13 was measured in cerebrospinal fluid (CSF) and serum of patients with NB (n1⁄428), systemic borreliosis (SB, n1⁄49), GuillaineBarré syndrome (GBS, n1⁄411), Bell’s palsy (BP, n1⁄419), other cranial nerve palsies (CNP, n1⁄45), cephalgia (C, n1⁄420), bacterial CNS infections (B-CNS-I, n1⁄416) and viral CNS infections (VCNS-I, n1⁄418). For follow-up studies, serial sample pairs were evaluated from 25 patients with NB (n1⁄456), 11 with B-CNS-I (n1⁄425) and 14 with V-CNS-I (n1⁄436). Results CSF-CXCL13 was significantly elevated in NB compared with other neurological diseases (p<0.001). Using receiver operating characteristic analysis, 337 ng/g was determined as a cut-off with a sensitivity of 96.4% and a specificity of 96.9%. Of all the parameters investigated, CSF CXCL13 showed the fastest response to antibiotic therapy, decreasing significantly (p1⁄40.008) within 1 week. In untreated patients, CSF CXCL13 was elevated in patients with a short duration of disease. Borrelia burgdorferi antibody index showed no significant (p1⁄40.356) change over follow-up. Conclusions The study confirms the relevance of CXCL13 as a diagnostic biomarker of NB and suggests that CSF CXCL13 in NB is linked to duration of disease and could be a marker of disease activity and response to antibiotic therapy. INTRODUCTION Neuroborreliosis (NB) is a nervous system manifestation of Lyme borreliosis, caused by the tickborne spirochete Borrelia burgdorferi (BB). Due to a great variety of neurological symptoms such as meningitis, meningoradiculitis or cranial nerve palsies, 6 identification of neuroborreliosis frequently is a diagnostic challenge in clinical neurology. Currently the method of choice for the diagnosis of acute NB is the combined analysis of basic cerebrospinal fluid (CSF) parameters (lymphocytic pleocytosis, intrathecal synthesis of immunoglobulins and/or bloodeCSF barrier dysfunction) and determination of BB-specific antibody index (BB-AI $1.5, ie, intrathecal antibody synthesis to BB). However, this approach has important limitations. First, elevated basic CSF variables are also found in various other inflammatory diseases of the central nervous system (CNS). 9 Second, intrathecal BB antibody synthesis may not be detectable in early stages of disease, especially if the disease duration is less than 2e3 weeks. Third, elevated BB-AI does not discriminate between active and past infections, as it is known to persist for years in spite of successful treatment. Fourth, false-positive results may occur due to antibody cross-reactivities. 15 16 Fifth, due to the use of different isolates as antigen in various immunosorbent assays for BB antibodies, results may vary considerably among different laboratories. Recent studies have suggested an important role of CXCL13 in the diagnosis of NB. 18 CXCL13 belongs to the CXC chemokine family and is a selective chemoattractant for B lymphocytes and B-helper T cells via the chemokine receptor CXCR5. Our aim was to confirm the diagnostic value of CXCL13 in NB in comparison with established diagnostic parameters such as BB-AI and to evaluate the relevance of CXCL13 as a marker of disease activity and therapy response in acute NB.