PURPOSE: Homing of malignant lymphocytes to the central nervous system (CNS) may play a role in the pathogenesis of CNS lymphoma. In this study, we evaluated the chemokines CXCL12 and CXCL13 in the cerebrospinal fluid (CSF) and serum of patients with CNS lymphoma. EXPERIMENTAL DESIGN: Samples from 30 patients with CNS lymphoma (23 with primary and 7 with secondary CNS lymphoma; all B-cell lymphoma) and 40 controls (10 patients with other CNS malignancies and 30 without a malignant CNS disease) were examined. CXCL12 and CXCL13 concentrations were measured using enzyme-linked immunosorbent assays. The grade of blood-brain barrier disruption was estimated by the CSF/serum albumin ratio. RESULTS: CNS lymphoma patients and controls did not differ in CXCL12 serum and CSF levels. Serum levels of CXCL13 were generally low. CXCL13 CSF levels, however, were significantly higher in CNS lymphoma patients as compared with controls (P < 0.0001). Chemokine levels in CSF and serum did not correlate. In CNS lymphoma, CXCL13 concentration in CSF correlated with the degree of blood-brain barrier disruption (R = 0.66; P = 0.003). Elevated CSF levels of CXCL12 and CXCL13 measured in seven CNS lymphoma patients during therapy decreased in five patients who responded to chemotherapy and increased in two with lymphoma progression. CONCLUSIONS: Our results suggest a production of CXCL13 within the CNS of CNS lymphoma patients, which decreases with response to therapy. Thus, CXCL13 may represent a marker for further diagnostic and prognostic studies.
PURPOSE: Homing of malignant lymphocytes to the central nervous system (CNS) may play a role in the pathogenesis of CNS lymphoma. In this study, we evaluated the chemokines CXCL12 and CXCL13 in the cerebrospinal fluid (CSF) and serum of patients with CNS lymphoma. EXPERIMENTAL DESIGN: Samples from 30 patients with CNS lymphoma (23 with primary and 7 with secondary CNS lymphoma; all B-cell lymphoma) and 40 controls (10 patients with other CNS malignancies and 30 without a malignant CNS disease) were examined. CXCL12 and CXCL13 concentrations were measured using enzyme-linked immunosorbent assays. The grade of blood-brain barrier disruption was estimated by the CSF/serum albumin ratio. RESULTS:CNS lymphomapatients and controls did not differ in CXCL12 serum and CSF levels. Serum levels of CXCL13 were generally low. CXCL13 CSF levels, however, were significantly higher in CNS lymphomapatients as compared with controls (P < 0.0001). Chemokine levels in CSF and serum did not correlate. In CNS lymphoma, CXCL13 concentration in CSF correlated with the degree of blood-brain barrier disruption (R = 0.66; P = 0.003). Elevated CSF levels of CXCL12 and CXCL13 measured in seven CNS lymphomapatients during therapy decreased in five patients who responded to chemotherapy and increased in two with lymphoma progression. CONCLUSIONS: Our results suggest a production of CXCL13 within the CNS of CNS lymphomapatients, which decreases with response to therapy. Thus, CXCL13 may represent a marker for further diagnostic and prognostic studies.
Authors: Johannes Brettschneider; Anne Czerwoniak; Makbule Senel; Lubin Fang; Jan Kassubek; Elmar Pinkhardt; Florian Lauda; Tamara Kapfer; Sarah Jesse; Vera Lehmensiek; Albert C Ludolph; Markus Otto; Hayrettin Tumani Journal: PLoS One Date: 2010-08-05 Impact factor: 3.240