title: CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma.
abstract: Establishing the diagnosis of focal brain lesions in patients with unexplained neurologic symptoms represents a challenge. The goal of this study is to provide evidence supporting functional roles for CXC chemokine ligand (CXCL)13 and interleukin (IL)-10 in central nervous system (CNS) lymphomas and to evaluate the utility of each as prognostic and diagnostic biomarkers. We demonstrate for the first time that elevated CXCL13 concentration in cerebrospinal fluid (CSF) is prognostic and that CXCL13 and CXCL12 mediate chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. Expression of the activated form of Janus kinase 1 supported a role for IL-10 in prosurvival signaling. We determined the concentration of CXCL13 and IL-10 in CSF of CNS lymphoma patients and control cohorts including inflammatory and degenerative neurologic disease in a multicenter study involving 220 patients. Bivariate elevated CXCL13 plus IL-10 was 99.3% specific for primary and secondary CNS lymphoma, with sensitivity significantly greater than reference standard CSF tests. These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration.
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. jamesr@medicine.ucsf.edu
authors.forename: James L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Wong
authors.forename: Cigall
authors.initials: C
authors.lastname: Kadoch
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Gao
authors.forename: Ramon
authors.initials: R
authors.lastname: Barajas
authors.forename: Lingjing
authors.initials: L
authors.lastname: Chen
authors.forename: S Andrew
authors.initials: SA
authors.lastname: Josephson
authors.forename: Brian
authors.initials: B
authors.lastname: Scott
authors.forename: Vanja
authors.initials: V
authors.lastname: Douglas
authors.forename: Mekhala
authors.initials: M
authors.lastname: Maiti
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Kaplan
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Treseler
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
authors.forename: Jimmy H
authors.initials: JH
authors.lastname: Hwang
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
authors.forename: Clifford
authors.initials: C
authors.lastname: Lowell
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid* / Q000235:genetics; D015153:Blotting, Western; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000401:mortality; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid* / Q000235:genetics; D002633:Chemotaxis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000134:cerebrospinal fluid* / Q000235:genetics; D008223:Lymphoma / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D012333:RNA, Messenger; D016753:Interleukin-10