ProCL – a prospective study on the role of CXCL13 in lyme neuroborreliosis

Background: Main clinical symptoms of Neuroborreliosis (NB) are painful meningopolyradiculitis, cranial neuritis or meningitis preceded by erythema migrans. However, due to high variability or atypical presentation of clinical symptoms diagnosis of NB can be difficult. The definitive diagnosis of acute NB requires the presence of a lymphomonocytic CSF pleocytosis and intrathecal B. burgdorferi (B.b.) specific antibody production (specific antibody index (AI) >1.5). However, positive AI is sometimes absent in early stages of the disease (up to 20%). Recent studies suggested an important role of a new biomarker CXCL13, a B-cell-attracting chemokine, in early NB. CXCL13 was found to be highly positive in initial CSF samples of patients with NB and therefore qualified as a valuable marker for early diagnosis and initiation of antibiotic therapy.

Goals: To prospectively assess the role of CXCL13 as a diagnostic marker in acute NB compared to B.b.-AI.

Patients and methods: Patients with CSF pleocytosis, in whom the responsible clinician had requested the B.b.-AI, were prospectively included into the study. After completion of routine CSF analysis, serum and CSF samples were stored at -20°C for further evalution: CXCL13 levels were determined in CSF and serum by ELISA. TPHA test will be performed to exclude crossreactivity due to infection with Treponema pallidum. In addition to the available clinical information patients were subjected to a standardized semistructured telephone interview. Written informed consent was obtained from all participants. The study was approved by the ethics committee.

Preliminary results and conclusion: Up to now (March 2009), samples from a total of 137 patients have been collected. CXCL13 ELISA has been performed in 67 patients (48.9%) so far. 7.5% of the analysed patients (n=5) had a B.b.-AI >1.5. Two of these patients had clinical symptoms of NB; both of them showed significantly elevated CXCL13 levels. By contrast, in two other patients without clinical symptoms of NB, CXCL13 levels were not increased. Finally, CXCL13 was not significantly elevated in another patient, who fulfilled the clinical criteria of acute NB, but who had been antibiotically treated before analysis.

All in all, our preliminary data confirm CXCL13 as a valuable diagnostic marker for acute NB; however, due to the limited case numbers, definite conclusions are not feasible at this point. The finalized data set will be presented at the congress.