CXCL12 and CXCL13 Levels in Cerebrospinal Fluid (CSF) of Patients with CNS Lymphoma.

Abstract

Background: The mechanisms leading to development of CNS lymphoma (CNSL) are still poorly understood. Homing of malignant lymphocytes to the CNS may play an important role in the pathogenesis of CNSL. Expression of chemokine receptors CXCR4 and CXCR5 has been shown on tumor cells of primary CNSL. In this study we examined the level of chemokines CXCL12 and CXCL13 which are ligands of CXCR4 and CXCR5 respectively in the CSF of CNSL patients and compared it to non-CNSL controls.Methods: Lumbar CSF and peripheral blood from 16 patients with primary and one with secondary CNSL, as well as control CSF from 8 patients with hydrocephalus, glioblastoma, peripheral lymphoma without CNS involvement or unspecific neurological symptoms were collected, and after centrifugation supernatant and serum were cryopreserved at −80°C until analysis. Chemokine concentrations were measured using commercially available ELISA kits (CXCL13/BCA-1 and CXCL12/SDF-1α Quantikine Immunoassay, R&D Systems, Minneapolis) according to the manufacturer's instructions. Results were confirmed by duplicate measurements.Results: 22 CSF samples and 11 serum samples from CNSL patients and nine CSF samples from controls were evaluated (see table). There was no correlation between serum and CSF chemokine levels in CNSL patients. Median concentrations of both CXCL12 and CXCR13 were higher in patients with CNS lymphoma compared to controls, CXCL13 being significantly raised (p=0.0019). In one CNSL patient three serial CSF samples could be analysed and a ten-fold decrease of CXCL12 during succesfull chemotherapy was found whilst concentration of CXCL13 remained stable.Conclusion: CXCL12 and CXCL13 can be measured in the CSF of CNS lymphoma patients at higher concentration as compared to non-CNSL patients. Analysis of a larger population is warranted in order to define the role of these chemokines in CNSL and to establish their value for diagnosis and follow up.SerumCSFCNSL patientsCNSL patientscontrolsprangemedian (range)median (range)CXCL121788–2933 pg/ml481 (55–2079) pg/ml115 (0–2442) pg/ml0.067CXCL1336–657 pg/ml457 (18–657) pg/ml16.9 (0.6–187) pg/ml0.00019