Cerebrospinal fluid CXCL13 in non-borrelial central nervous system infections: contribution of CXCL13 to the differential diagnosis

Abstract

Background The chemokine CXCL13 in cerebrospinal fluid (CSF) is used as a diagnostic marker of Lyme neuroborreliosis (LNB). However, the elevated levels in other non-borrelial CNS infections and the lack of a clearly defined cut-off value are limitations of the test. Methods In our prospective study, we evaluated CSF CXCL13 levels in patients with LNB (47 patients), tick-borne encephalitis (TBE; 46 patients), enteroviral CNS infections (EV; 45 patients), herpetic CNS infections (HV; 23 patients), neurosyphilis (NS; 11 patients) and controls (46 patients). The correlation of CXCL13 with CSF mononuclears was determined in all groups. Results Median CXCL13 was significantly higher in LNB group; however, the cut-off value of 162 pg/mL was also exceeded in 22% of TBE patients, 2% EV patients, 44% HV patients and in 55% patients with NS. Sensitivity and specificity were 0.83 and 0.78, respectively, with a Youden index of 0.62. CXCL13 was significantly correlated with CSF mononuclears (p = .0024), but the type of infectious agent had a greater influence on CXCL13 levels. Conclusions Increased CXCL13 levels are useful for LNB diagnostics, but other non-purulent CNS infections causes should be considered if intrathecal synthesis of borrelia specific antibodies is not confirmed or clinical manifestations are atypical.