Highly sensitive quantification of optic neuritis intrathecal biomarker CXCL13

Olesen, Mads Nikolaj; Nilsson, Anne; Pihl-Jensen, Gorm; Soelberg, Kerstin; Olsen, Dorte Aalund; Brandslund, Ivan; Lillevang, S T; Madsen, Jonna Skov; Frederiksen, Jette Lautrup; Asgari, Nasrin

doi:10.1016/j.msard.2020.102281

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…It is still unclear whether TLOs exist during the acute course of the disease or are formed only during chronification [ 67 ]. Additionally, in patients who developed RRMS after CIS or optic neuritis, CSF-CXCL13 was significantly higher [ 45 , 65 , 69 , 70 ]. Multiple sclerosis/CIS patients with clinical or radiographic relapse symptoms, gadolinium-enhancing T1 lesions, or enlarging T2 lesions in MRI had elevated CSF-CXCL13 levels compared to those in patients with primary or secondary progressive MS (PPMS/SPMS) [ 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

CXCL13 in Cerebrospinal Fluid: Clinical Value in a Large Cross-Sectional Study

Erhart,

Klose,

Schäper

et al. 2023

IJMS

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C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent cut-off values have been defined so far mainly for neuroborreliosis. Our aim was to evaluate the value of CSF-CXCL13 as a diagnostic and treatment response marker and its role as an activity marker in a larger disease spectrum, including neuroborreliosis and other neuroinflammatory and malignant CNS-disorders. Patients who received a diagnostic lumbar puncture (LP) (n = 1234) between July 2009 and January 2023 were included in our retrospective cross-sectional study. The diagnostic performance of CSF-CXCL13 for acute neuroborreliosis was highest at a cut-off of 428.92 pg/mL (sensitivity: 92.1%; specificity: 96.5%). In addition, CXCL13 levels in CSF were significantly elevated in multiple sclerosis with clinical (p = 0.001) and radiographic disease activity (p < 0.001). The clinical utility of CSF-CXCL13 appears to be multifaceted. CSF-CXCL13 is significantly elevated in patients with neuroborreliosis and shows a rapid and sharp decline with antibiotic therapy, but it is not specific for this disease and is also highly elevated in less common subacute neuroinfectious diseases, such as neurosyphilis and cryptococcal meningitis or in primary/secondary B-cell lymphoma.

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Section: Discussionmentioning

confidence: 99%

CXCL13 in Cerebrospinal Fluid: Clinical Value in a Large Cross-Sectional Study

Erhart,

Klose,

Schäper

et al. 2023

IJMS

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“…However, in our lab and in others [ 77 ], ELISA has proven to have inadequate sensitivity. Thus, ELISA is not an optimal method of detection of CSF CXCL13 in MS. Other methodologies for assaying CXCL13 in CSF and serum have been used, including immunoPCR [ 78 ], and SIMOA [ 79 ], but these are not readily available for most clinical laboratories. However, an accurate and reliable methodology for assaying CXCL13 in the CSF is Luminex ( , accessed on 13 July 2022), a microsphere-based technology with increasing use in the clinical laboratory.…”

Section: Two Logical Candidates For Molecular Biomarkers Based On The...mentioning

confidence: 99%

The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy

Pachner

2022

Biomedicines

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Multiple sclerosis (MS) is a highly heterogeneous disease involving a combination of inflammation, demyelination, and CNS injury. It is the leading cause of non-traumatic neurological disability in younger people. There is no cure, but treatments in the form of immunomodulatory drugs (IMDs) are available. Experience over the last 30 years has shown that IMDs, also sometimes called disease-modifying therapies, are effective in downregulating neuroinflammatory activity. However, there are a number of negatives in IMD therapy, including potential for significant side-effects and adverse events, uncertainty about long-term benefits regarding disability outcomes, and very high and increasing financial costs. The two dozen currently available FDA-approved IMDs also are heterogeneous with respect to efficacy and safety, especially long-term safety, and determining an IMD treatment strategy is therefore challenging for the clinician. Decisions about optimal therapy have been particularly difficult in early MS, at the time of the initial clinical demyelinating event (ICDE), at a time when early, aggressive treatment would best be initiated on patients destined to have a highly inflammatory course. However, given the fact that the majority of ICDE patients have a more benign course, aggressive immunosuppression, with its attendant risks, should not be administered to this group, and should only be reserved for patients with a more neuroinflammatory course, a decision that can only be made in retrospect, months to years after the ICDE. This quandary of moderate vs. aggressive therapy facing clinicians would best be resolved by the use of biomarkers that are predictive of future neuroinflammation. Unfortunately, biomarkers, especially molecular biomarkers, have not thus far been particularly useful in assisting clinicians in predicting the likelihood of future neuroinflammation, and thus guiding therapy. However, the last decade has seen the emergence of two highly promising molecular biomarkers to guide therapy in early MS: the CXCL13 index and neurofilament light. This paper will review the immunological and neuroscientific underpinnings of these biomarkers and the data supporting their use in early MS and will propose how they will likely be used to maximize benefit and minimize risk of IMDs in MS patients.

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CSF CXCL13 and Chitinase 3-like-1 Levels Predict Disease Course in Relapsing Multiple Sclerosis

et al. 2022

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Several biomarkers from multiple sclerosis (MS) patients’ biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Considering RMS patients with a single demyelinating event, higher concentrations of CHI3L1, CXCL10, CXCL12, and CXCL13 were recorded in patients who converted to clinically defined MS(CDMS). RMS patients in the CXCL13 and CHI3L1 high concentration group had a significantly higher risk of relapse (HR 12.61 and 4.57), MRI activity (HR 7.04 and 2.46), and of any evidence of disease activity (HR 12.13 and 2.90) during follow-up. CSF CXCL13 and CHI3L1 levels represent very good prognostic biomarkers in RMS patients, and therefore can be helpful in the treatment choice. Higher CSF concentrations of neuro-inflammatory biomarkers were associated with a higher risk of conversion to CDMS in patients with a first clinical demyelinating event. Differential CSF BAFF and APRIL levels between RMS and PMS suggest a different modulation of B-cells pathways in the different phases of the disease.

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Highly sensitive quantification of optic neuritis intrathecal biomarker CXCL13

Cited by 3 publications

References 32 publications

CXCL13 in Cerebrospinal Fluid: Clinical Value in a Large Cross-Sectional Study

CXCL13 in Cerebrospinal Fluid: Clinical Value in a Large Cross-Sectional Study

The Brave New World of Early Treatment of Multiple Sclerosis: Using the Molecular Biomarkers CXCL13 and Neurofilament Light to Optimize Immunotherapy

CSF CXCL13 and Chitinase 3-like-1 Levels Predict Disease Course in Relapsing Multiple Sclerosis

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