Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS

Sellebjerg, Finn; Börnsen, Lars; Khademi, Mohsen; Krakauer, Martin; Olsson, Tomas; Frederiksen, Jette Lautrup; Sørensen, Per

doi:10.1212/wnl.0b013e3181c5b457

Cited by 195 publications

(172 citation statements)

References 42 publications

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“…However, a diagnostic method should not depend on mere differences in incidence rates. Furthermore, increased levels of CSF-CXCL13 have also been reported in MS, albeit at lower levels, in general, compared with LNB (12)(13)(25)(26)(27). Although CXCL13 in CSF is a more specific marker for LNB compared to pleocytosis, which may be found in many other central nervous system diseases such as bacterial and viral meningitis and various inflammatory central nervous system diseases (13), the increased CXCL13 levels found in MS and NS point to the benefit of combining results of CXCL13 with intrathecally produced anti-borrelia antibodies in order to gain diagnostic specificity.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis

Tjernberg

Henningsson

Eliasson

et al. 2011

Journal of Infection

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Section: Discussionmentioning

confidence: 99%

Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis

Tjernberg

Henningsson

Eliasson

et al. 2011

Journal of Infection

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“…CXCL13 concentration in CSF was also elevated in 6 of 11 subjects with CNS demyelinating disease (9-116 pg/mL), consistent with previous observations. 25 Of note, CXCL13 concentration was also elevated in the CSF of 3 of 6 patients with breast cancer metastatic to the brain (58-508 pg/mL), suggesting a role for this chemokine in directional migration of breast cancer cells to the brain 26 (Table 1; supplemental Tables 1-3). We noted that newly diagnosed patients with CNS involvement of lymphoma (both primary and secondary) with low CSF levels of CXCL13 at diagnosis (below the median concentration of 200 pg/mL) exhibited significantly longer progression-free survival (PFS) with standardized treatment 27 compared with newly diagnosed patients with high CSF CXCL13, suggesting a physiological role for this chemokine in CNS lymphoma pathogenesis ( Figure 2).…”

Section: Cxcl13 and Il-10 In The Diagnosis Of Cns Lymphoma 4741mentioning

confidence: 99%

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

Rubenstein

Wong

Kadoch

et al. 2013

Blood

192

174

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Key Points• CXCL13 and CXCL12 mediate chemotaxis of CNS lymphoma cells, and CXCL13 concentration in CSF is prognostic.• CXCL13 plus IL-10 is highly specific for the diagnosis of CNS lymphoma.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. (Blood. 2013;121(23):4740-4748) IntroductionDetermination of the pathological basis of focal brain lesions in patients with unexplained neurologic symptoms is a major clinical challenge. Persistent symptoms or rapid neurologic decline often mandates stereotactic brain biopsy, a highly invasive procedure with a 10% to 35% rate of diagnostic failure.1-3 Moreover, many lesions are not amenable to biopsy because of small size, location in deep brain structures, risk of hemorrhage, and other comorbidities.The diagnosis of central nervous system (CNS) involvement of non-Hodgkin lymphoma is a particular challenge because of lesional response to glucocorticoids and features on magnetic resonance imaging (MRI) that are shared with other pathologies including astrocytic neoplasms, demyelination, neurosarcoid, vasculitis, infections, and leptomeningeal dissemination of systemic cancer. Although flowcytometric and cytological analysis of cerebrospinal fluid (CSF) is useful in the evaluation of leptomeningeal disease, these tests are usually insensitive to pathological processes based in deep brain structures and rarely provide information that eliminates the need for brain biopsy; the sensitivity of CSF cytological analysis in the evaluation of primary CNS lymphoma (PCNSL) is ;15%. 4Advances that facilitate diagnosis and early treatment of CNS lymphoma would likely be cost-effective, minimize repeat diagnostic CSF and MRI evaluations and brain biopsies, and also lead to improved outcomes. [5][6][7] The molecular const...

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“…CXCL13 has recently been reported as a biomarker useful to discriminate MS from other non-inflammatory neurological diseases and thus for diagnostic purposes. [30][31][32] This T and B cell-attracting chemokine is probably not elevated when compared to inflammatory neurological diseases. Interestingly, CXCL13 level was increased in CIS converting to clinically definite MS and a correlation with EDSS score was also reported.…”

Section: Recently Reported Candidate Biomarkers For Disease Progressionmentioning

confidence: 99%

Neurofilaments as biomarkers in multiple sclerosis

2012

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Neurodegeneration is the correlate of disease progression in multiple sclerosis (MS) and thus biological biomarkers that sensitively reflect this process are much needed. Neurofilament protein subunits are potential cerebrospinal fluid (CSF) biomarkers for disease progression in MS. We argue that the neurofilament light subunit can reflect acute axonal damage mediated by inflammatory mechanisms and can imply prognostic value for conversion from clinically isolated syndrome (CIS) to definite MS. The neurofilament heavy subunit may rather reflect chronic irreversible damage and has prognostic value for disease progression or disability. The neurofilament intermediate subunit has not yet been studied. Recent studies showing higher neurofilament light or heavy subunit levels to be altered upon treatment regimes indicate their potential clinical value in monitoring treatment or side effects. Future studies should be aimed at the optimisation, standardisation and interlaboratory implementation of the assays and address the predictive value of these biomarkers.

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Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS

Cited by 195 publications

References 42 publications

Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis

Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis

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

Neurofilaments as biomarkers in multiple sclerosis

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