High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease

Bugatti, Serena; Manzo, Antonio; Vitolo, Barbara; Benaglio, Francesca; Binda, Elisa; Scarabelli, M.; Humby, Frances; Caporali, Roberto; Pitzalis, Costantino; Montecucco, Carlomaurizio

doi:10.1093/rheumatology/keu163

Cited by 68 publications

(73 citation statements)

References 50 publications

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“…Accordingly, synovial levels of CXCL13 expression and lymphocyte infiltration appear associated with features of local disease activity in early RA [100, 107], whilst the correlation is weaker or even lost for longer duration [106, 107, 110]. Thus, “B-cell synovitis” does not per se appear synonymous to clinically active disease.…”

Section: B Cells As Biomarkersmentioning

confidence: 99%

“…A recent study comparing the effects of tocilizumab with methotrexate failed to report significant changes in B cell and plasma cell numbers in 15 patients with early RA receiving standard dosages of MTX for 6 months [123]. Relevantly, gene expression levels of CXCL13 also remained unchanged [123], confirming that this chemokine may be a marker of more refractory synovitides with worst disease evolution upon conventional treatments [104–107]. In contrast to synthetic DMARDs, biological drugs may interfere with local B-cell pathology.…”

Section: B Cells As Biomarkersmentioning

confidence: 99%

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B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

Bugatti

Vitolo

Caporali

et al. 2014

BioMed Research International

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137

113

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The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has refocused attention on B cells with increasing awareness on their role in autoimmunity and their function beyond autoantibody production. The rapid increase in our comprehension of B-cell pathobiology is progressively opening novel perspectives in the area of B cell-targeted therapies with the expectation to define more specific approaches able to preserve the homeostasis of the humoral response while disrupting the pathogenic components. In parallel, B-cell activity in RA is starting to be explored in its clinical value, in search of novel biomarkers embedded in the pathogenic process that could help classifying the disease and predicting its heterogeneous outcome beyond inflammation dynamics. In this review, we summarize current knowledge on the multiple roles that B cells play in several aspects of RA. We also analyze their distribution and potential function in different anatomic compartments with specific reference to the main sites in which the disease may be sustained and exert its detrimental effects: the systemic circulation, synovium, bone marrow, and draining lymph nodes. We also highlight novel data encouraging further research in the field of biomarkers related to B cells and their regulatory factors.

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Section: B Cells As Biomarkersmentioning

confidence: 99%

Section: B Cells As Biomarkersmentioning

confidence: 99%

B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

Bugatti

Vitolo

Caporali

et al. 2014

BioMed Research International

Self Cite

137

113

View full text Add to dashboard Cite

show abstract

“…patients correlates with more severe disease (22). Likewise, serum CXCL13 correlates with synovial CXCL13 measured at a single joint, suggesting synovitis as an important source of circulating CXCL13.…”

Section: Genetic Associations With Anti-tnf-responsementioning

confidence: 86%

Integration of Known DNA, RNA and Protein Biomarkers Provides Prediction of Anti-TNF Response in Rheumatoid Arthritis: Results from the COMBINE Study

Folkersen

Brynedal

Diaz-Gallo

et al. 2016

Mol Med

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and 5 Current affiliation: AbbVie, Copenhagen, Denmark; *These senior authors contributed equally OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients. METHODS: We collected 451 blood samples from 61 healthy individuals and 185 RA patients initiating treatment, before treatment initiation and at a 3 month follow-up time. All samples were subjected to high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as predictors of Tumor Necrosis Factor (TNF) inhibitor response (ΔDAS28-CRP). RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the variation in ΔDAS28-CRP. This corresponds to a sensitivity of 0.73 and specificity of 0.78 for the prediction of three month ΔDAS28-CRP better than -1.2. CONCLUSIONS: The COMBINE biobank is currently the largest collection of multi-omics data from RA patients with high potential for discovery and replication. Taking advantage of this we surveyed the current state-of-the-art of drug-response stratification in RA, and identified a small set of previously published biomarkers available in peripheral blood which predicts clinical response to TNF blockade in this independent cohort. online address: http://www.molmed.org

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“…При изучении локальной и системной продукции ФПСК1 и ХВК1 было установлено, что больные серопози-тивным РА характеризуются повышением уровня ХВК1 в сыворотке крови, в то время как уровень экспрессии дан-ного белка клетками СО коррелировал как с выраженно-стью системного воспаления, так и с интенсивностью ло-кального воспалительного процесса и содержанием РФ [10]. Уровни ФПСК1 также были повышены в сыворотке синовиальной жидкости, СО больных РА и коррелировали с уровнем АЦЦП [11,12].…”

Section: Discussionunclassified

Comparison of the Diagnostic Informative Value of Determination of Mrna of Some Homeostatic and Proinflammatory Cytokines in the Synovial Membrane of Patients With Rheumatoid Arthritis

Маслянский¹,

Жебрун²,

Титов³

et al. 2016

rsp

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High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease

Abstract: Synovial CXCL13 appears to be a marker of a more severe pattern of RA disease, characterized by increased lymphocyte activation and bone remodelling beyond the level of conventional markers of inflammation.

Cited by 68 publications

References 50 publications

B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

Integration of Known DNA, RNA and Protein Biomarkers Provides Prediction of Anti-TNF Response in Rheumatoid Arthritis: Results from the COMBINE Study

Comparison of the Diagnostic Informative Value of Determination of Mrna of Some Homeostatic and Proinflammatory Cytokines in the Synovial Membrane of Patients With Rheumatoid Arthritis

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