The Chemokine CXCL13 Is a Prognostic Marker in Clinically Isolated Syndrome (CIS)

Brettschneider, Johannes; Czerwoniak, Anne; Şenel, Makbule; Fang, Lubin; Kassubek, Jan; Pinkhardt, Elmar H.; Lauda, Florían; Kapfer, Tamara; Jesse, Sarah; Lehmensiek, Vera; Ludolph, Albert C.; Otto, Markus; Tumani, Hayrettin

doi:10.1371/journal.pone.0011986

Cited by 121 publications

(115 citation statements)

References 42 publications

(68 reference statements)

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“…In conjunction with demonstrations that the circulating B cells of patients with IPF are not uniquely ORIGINAL ARTICLE deficient in their expression of the chemotactic ligand CXCR5 (Figure 2), and numerous definitive reports in other populations (31)(32)(33)(34)(35)(36), it is thus highly likely the CXCL13-CXCR5 axis is involved in the focal accumulations of nonproliferating B cells that were found in IPF lungs here and in other studies (3)(4)(5) Figure 4). The longitudinal CXCL13 assays here ( Figure 5) support the validity of these cross-sectional observations.…”

Section: Discussionsupporting

confidence: 79%

“…The findings in these subjects with IPF parallel analogous observations in patients with other syndromes that are known to be mediated by pathologic B cells (31)(32)(33). Given the lack of progress in the treatment of IPF, which remains a highly morbid and almost invariably fatal disease (1), objective considerations of pathogenic paradigms that could illuminate new therapeutic approaches for this disease seem warranted.…”

Section: Discussionmentioning

confidence: 54%

“…C-X-C motif chemokine 13 (CXCL13) is a critical agent for B-cell homing to inflammatory foci that is implicated in the pathogenesis of several immunologic disorders (31)(32)(33)(34)(35). Circulating CXCL13 is increased in many classical autoimmune syndromes, and levels of this chemokine are often correlated with the clinical activity of these diseases (31)(32)(33).…”

mentioning

confidence: 99%

“…Circulating CXCL13 is increased in many classical autoimmune syndromes, and levels of this chemokine are often correlated with the clinical activity of these diseases (31)(32)(33). The B-cell ligand for CXCL13 that mediates lymphocyte chemotaxis is C-X-C chemokine receptor 5 (CXCR5) (36).…”

mentioning

confidence: 99%

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C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Vuga¹,

Tedrow²,

Pandit³

et al. 2014

Am J Respir Crit Care Med

163

115

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Rationale: C-X-C motif chemokine 13 (CXCL13) mediates B-cell trafficking and is increased, proportionately to disease activity, in many antibody-mediated syndromes. Dysregulated B cells have recently been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis.Objectives: To determine if CXCL13 is associated with IPF progression.Methods: CXCL13 was measured in lungs by DNA microarray and immunohistochemistry, and in plasma by ELISA.Measurements and Main Results: CXCL13 mRNA was threefold and eightfold greater in IPF lungs (n = 92) compared with chronic obstructive pulmonary disease (COPD) (n = 191) and normal (n = 108) specimens, respectively (P , 0.0001). IPF lungs also showed increased CXCL13 staining. Plasma CXCL13 concentrations (pg/ml) were greater in 95 patients with IPF (94 6 8) than in 128 subjects with COPD (53 6 9) and 57 normal subjects (35 6 3) (P , 0.0001). Circulating CXCL13 levels were highest in patients with IPF with pulmonary artery hypertension (P = 0.01) or acute exacerbations (P = 0.002). Six-month survival of patients with IPF in the highest quartile of plasma CXCL13 was 65 6 10% versus 93 6 10% in the others (hazard ratio, 5.5; 95% confidence interval, 1.8-16.9; P = 0.0008). CXCL13 increases by more than 50% in IPF serial assays, irrespective of initial values, also presaged respiratory failure (hazard ratio, 7.2; 95% confidence interval, 1.3-40.0; P = 0.008). In contrast, CXCL13 clinical associations in subjects with COPD were limited to modest correlations with FEV 1 (P = 0.05) and progression of radiographic emphysema (P = 0.05).Conclusions: CXCL13 is increased and is a prognostic biomarker in patients with IPF, and more so than in patients with COPD. This contrast indicates CXCL13 overexpressions are intrinsic to IPF, rather than an epiphenomenon of lung injury. The present data implicate CXCL13 and B cells in IPF pathogenesis, and support considerations for trials of specific B-cell-targeted therapies in patients with this intractable disease.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 99%

mentioning

confidence: 99%

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C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Vuga¹,

Tedrow²,

Pandit³

et al. 2014

Am J Respir Crit Care Med

163

115

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“…CXCL13 is produced by stromal cells and influences the migration of B cells (12). Previous studies have shown elevated concentrations of CXCL13 in the CSF samples of patients with Lyme neuroborreliosis, multiple sclerosis, and some other inflammatory diseases (11,(13)(14)(15)(16), suggesting that CXCL13 is a diagnostic marker for Lyme neuroborreliosis (17,18). As has been indicated by some reports, elevated concentrations of CXCL13 in the CSF may appear several days before intrathecal borrelial antibody synthesis occurs (18,19).…”

mentioning

confidence: 85%

Diagnostic Value of Cytokines and Chemokines in Lyme Neuroborreliosis

Cerar

Ogrinc

Lotrič‐Furlan

et al. 2013

Clin. Vaccine Immunol.

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The aims of the present study were to assess the concentrations of different cytokines and chemokines in blood serum and cerebrospinal fluid (CSF) samples of patients with Lyme neuroborreliosis and to identify the possible marker(s) that would enable a distinction between clinically evident and suspected Lyme neuroborreliosis, as well as between Lyme neuroborreliosis and tickborne encephalitis (TBE). Our additional interest was to evaluate the relationship between cytokine and chemokine concentrations and Borrelia burgdorferi sensu lato isolation from CSF, as well as intrathecal synthesis of specific borrelial antibodies. We found that higher concentrations of CXCL13 and lower concentrations of interleukin 10 (IL-10) in serum were associated with higher odds for clinically evident Lyme neuroborreliosis compared to suspected Lyme neuroborreliosis, as well as to TBE. The concentrations of IL-2, IL-5, IL-6, IL-10, and CXCL13 in the CSF were higher in patients with evident Lyme neuroborreliosis than in those who were only suspected to have the disease. A comparison of CSF cytokine and chemokine levels in patients with and without intrathecal synthesis of specific borrelial antibodies revealed that CXCL13 CSF concentration is significantly associated with intrathecal synthesis of borrelial antibodies. A comparison of the cytokine and chemokine CSF concentrations in patients with clinically evident Lyme neuroborreliosis according to CSF culture results revealed that higher concentrations of gamma interferon (IFN-␥) were associated with lower odds of Borrelia isolation. Although several differences in the blood serum and CSF concentrations of various cytokines and chemokines between the groups were found, the distinctive power of the majority of these findings is low. Further research on well-defined groups of patients is needed to appraise the potential diagnostic usefulness of these concentrations.

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A multi‐biomarker follow‐up study of patients with multiple sclerosis

et al. 2016

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ObjectivesThis study aimed to examine the levels of the macrophage marker sCD163 and other biomarkers at the time of diagnosis of patients with either clinically isolated syndrome (CIS) or relapsing‐remitting multiple sclerosis (RRMS), and assess relation to clinical indicators of prognosis, disease activity (DA), and changes in the levels of these biomarkers at follow‐up.Materials and MethodsThe clinical status and MRI were reevaluated in 56 patients more than 1 year after diagnosis with a median follow‐up time of 2 years. Levels of biomarkers in serum and cerebrospinal fluid (CSF) samples were evaluated by enzyme‐linked immunosorbent assays.ResultsThere was no significant difference in time to DA between patients with CIS and RRMS. A high sCD163 ratio (>0.07) was significantly (P = 0.04) associated with time to DA in the untreated patient group. In 21 patients reevaluated with serum and CSF samples, the sCD163 ratio levels decreased from 0.068 to 0.054 (P = 0.026) in the CIS/RRMS‐treated group. The CSF CXCL13, CXCL13 ratio, CSF neurofilament light polypeptide and osteopontin levels also decreased significantly in the CIS/RRMS‐treated group.ConclusionsThe levels of all biomarkers changed concurrently with MS treatment. The sCD163 ratio was identified as a potential novel marker for time to DA.

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The Chemokine CXCL13 Is a Prognostic Marker in Clinically Isolated Syndrome (CIS)

Cited by 121 publications

References 42 publications

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Diagnostic Value of Cytokines and Chemokines in Lyme Neuroborreliosis

A multi‐biomarker follow‐up study of patients with multiple sclerosis

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