CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma.

James L. Rubenstein, Valerie S. Wong, Cigall Kadoch, Hua Xin Gao, Ramon Barajas, Lingjing Chen, S. Andrew Josephson, Brian Scott, Vanja Douglas, Mekhala Maiti, Lawrence D. Kaplan, Patrick A. Treseler, Soonmee Cha, Jimmy H. Hwang, Paola Cinque, Jason G. Cyster, Clifford Lowell

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4740-4748
Number of pages9
JournalBlood
Volume121
Issue number23
DOIs
StatePublished - Jun 6 2013
Externally publishedYes

Fingerprint

Neurology
Interleukin-10
Lymphoma
Central Nervous System
Cerebrospinal fluid
Cerebrospinal Fluid
Biomarkers
Brain
Janus Kinase 1
CXC Chemokines
Chemotaxis
Neurologic Manifestations
Neurodegenerative Diseases
Multicenter Studies
Ligands

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Rubenstein, J. L., Wong, V. S., Kadoch, C., Gao, H. X., Barajas, R., Chen, L., ... Lowell, C. (2013). CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood, 121(23), 4740-4748. https://doi.org/10.1182/blood-2013-01-476333

CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. / Rubenstein, James L.; Wong, Valerie S.; Kadoch, Cigall; Gao, Hua Xin; Barajas, Ramon; Chen, Lingjing; Josephson, S. Andrew; Scott, Brian; Douglas, Vanja; Maiti, Mekhala; Kaplan, Lawrence D.; Treseler, Patrick A.; Cha, Soonmee; Hwang, Jimmy H.; Cinque, Paola; Cyster, Jason G.; Lowell, Clifford.

In: Blood, Vol. 121, No. 23, 06.06.2013, p. 4740-4748.

Research output: Contribution to journalArticle

Rubenstein, JL, Wong, VS, Kadoch, C, Gao, HX, Barajas, R, Chen, L, Josephson, SA, Scott, B, Douglas, V, Maiti, M, Kaplan, LD, Treseler, PA, Cha, S, Hwang, JH, Cinque, P, Cyster, JG & Lowell, C 2013, 'CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma.', Blood, vol. 121, no. 23, pp. 4740-4748. https://doi.org/10.1182/blood-2013-01-476333
Rubenstein, James L. ; Wong, Valerie S. ; Kadoch, Cigall ; Gao, Hua Xin ; Barajas, Ramon ; Chen, Lingjing ; Josephson, S. Andrew ; Scott, Brian ; Douglas, Vanja ; Maiti, Mekhala ; Kaplan, Lawrence D. ; Treseler, Patrick A. ; Cha, Soonmee ; Hwang, Jimmy H. ; Cinque, Paola ; Cyster, Jason G. ; Lowell, Clifford. / CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. In: Blood. 2013 ; Vol. 121, No. 23. pp. 4740-4748.
@article{666cc1399c6843fd8acc276b856b0662,
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.",
author = "Rubenstein, {James L.} and Wong, {Valerie S.} and Cigall Kadoch and Gao, {Hua Xin} and Ramon Barajas and Lingjing Chen and Josephson, {S. Andrew} and Brian Scott and Vanja Douglas and Mekhala Maiti and Kaplan, {Lawrence D.} and Treseler, {Patrick A.} and Soonmee Cha and Hwang, {Jimmy H.} and Paola Cinque and Cyster, {Jason G.} and Clifford Lowell",
year = "2013",
month = "6",
day = "6",
doi = "10.1182/blood-2013-01-476333",
language = "English (US)",
volume = "121",
pages = "4740--4748",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "23",

}

TY - JOUR

T1 - CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma.

AU - Rubenstein, James L.

AU - Wong, Valerie S.

AU - Kadoch, Cigall

AU - Gao, Hua Xin

AU - Barajas, Ramon

AU - Chen, Lingjing

AU - Josephson, S. Andrew

AU - Scott, Brian

AU - Douglas, Vanja

AU - Maiti, Mekhala

AU - Kaplan, Lawrence D.

AU - Treseler, Patrick A.

AU - Cha, Soonmee

AU - Hwang, Jimmy H.

AU - Cinque, Paola

AU - Cyster, Jason G.

AU - Lowell, Clifford

PY - 2013/6/6

Y1 - 2013/6/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84881057567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881057567&partnerID=8YFLogxK

U2 - 10.1182/blood-2013-01-476333

DO - 10.1182/blood-2013-01-476333

M3 - Article

C2 - 23570798

AN - SCOPUS:84881057567

VL - 121

SP - 4740

EP - 4748

JO - Blood

JF - Blood

SN - 0006-4971

IS - 23

ER -