Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis

Bao, Yu-Qing; Wang, Junping; Dai, Ziwei; Mao, Yan-Mei; Wu, Jun; Guo, Heng-Sheng; Xia, Yuan-Rui; Ye, Dong-Qing

doi:10.1007/s10067-019-04775-z

Cited by 22 publications

(18 citation statements)

References 37 publications

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“…CXCL13, CXCL10, CXCL6 and CXCL3 are the main members of the CXC chemokine subfamily. C-X-C motif chemokine ligand 13 (CXCL13), a B cell chemokine, interacting with its receptor C-X-C motif chemokine receptor 5 (CXCR5) promotes the migration and aggregation of B lymphocytes [33]. The expression level of CXCL13 with the serum of RA patients are positively correlated with the level of rheumatoid factor, and is also correlated with the disease activity and treatment response of early rheumatoid arthritis [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq and Network Analysis Reveal Unique Chemokine Activity Gene Expression Signatures in Synovial Tissue From Rheumatoid Arthritis

Zhang¹,

Jin²,

Chang³

et al. 2021

Preprint

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Objective: This study identified to provide a comprehensive understanding of genome-wide expression patterns of synovial tissue from rheumatoid arthritis (RA) patients to investigate the potential mechanism RA occurrence and development. Methods: The transcription profiles of 9 RA and 15 control (osteoarthritis OA) synovial tissue were generated by RNA-Seq. Gene set enrichment analysis (GSEA) was used to analyze all detected genes and differentially expressed genes (DEGs) were identified by DESeq. To further analyze the DEGs, Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. The protein-protein interaction (PPI) network of DEGs were constructed by STRING and the hub genes were identified by topology clustering with MCODE-Cytoscape. The most important hub genes were validated by quantitative real time polymerase chain reaction (qRT-PCR). Results: A total of 17736 genes were detected and 651 DEGs were identified. For the GSEA, significantly enriched gene sets positively correlated with the RA group were CD40 signaling over-activation, Th1 cytotoxic module in C2, over-activation of immune response, adaptive immune response in C5, In C7, the up-regulation of the gene set of effective versus memory CD8 T cell is related to RA group. The down-regulation of gene set of naïve versus effective CD8 T cell is related to RA group.in C7. Biology process enrichment analysis showed that the DEGs were significantly enriched for signal transduction (P=1.52×10-08), immune response (P=1.94×10-22) and inflammatory response (P=1.11×10-11). Molecule function enrichment analysis revealed over-represented calcium ion binding (P=8.61×10-03), receptor binding (P=7.03×10-05) and chemokine activity (P=4.15×10-15). The DEGs were significantly enriched for plasma membrane (P=2.26×10-20), integral component of membrane (P=7.79×10-07), extracellular region (P=3.43×10-16) in cellular component. The KEGG pathway analysis showed that the DEGs were enriched in the cytokine-cytokine receptor interaction (P=6.86×10-21), chemokine signaling pathway (P=2.03×10-11), systemic lupus erythematosus(P=9.23×10-07), T cell receptor signaling pathway (P=6.59×10-06) and rheumatoid arthritis (P=3.24×10-05). We confirmed RA over-expressed PPI network hub genes included CXCL13, CXCL6, CCR5, CXCR5, CCR2, CXCL3, CXCL10 and RA down-regulated hub genes included SSTR1. Conclusions: The study identified and verified the DEGs between RA and OA synovial tissue which highlighted the activity of a subset of chemokine genes, thereby providing novel insights into the molecular mechanisms of RA pathogenesis and identified potential diagnostic and therapeutic targets for RA.

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Section: Discussionmentioning

confidence: 99%

RNA-Seq and Network Analysis Reveal Unique Chemokine Activity Gene Expression Signatures in Synovial Tissue From Rheumatoid Arthritis

Zhang¹,

Jin²,

Chang³

et al. 2021

Preprint

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“…Indeed, mice with a whole-body CXCR5 knockout display defects in secondary lymphoidtissue architecture (Fö rster et al, 1996). As our understanding of the CXCL13-CXCR5 axis continues to grow, it is becoming clearer that this interacting pair may represent a valuable drug target in multiple disease conditions, including autoimmune disorders and cancers (Airoldi et al, 2008;Biswas et al, 2014;Bü rkle et al, 2007;Charbonneau et al, 2013;El-Haibi et al, 2011Singh et al, 2009Singh et al, , 2014Dupuis et al, 2006;Bao et al, 2020;Klimatcheva et al, 2015). Despite this, no drug candidates have successfully been developed to target the receptor, nor are there any structural data on the receptor to aid in their development.…”

Section: Discussionmentioning

confidence: 99%

The N-terminal length and side-chain composition of CXCL13 affect crystallization, structure and functional activity

Rosenberg

Herrington²,

Rajasekaran

et al. 2020

Acta Cryst Sect D Struct Biol

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CXCL13 is the cognate chemokine agonist of CXCR5, a class A G-protein-coupled receptor (GPCR) that is essential for proper humoral immune responses. Using a `methionine scanning' mutagenesis method on the N-terminus of CXCL13, which is the chemokine signaling region, it was shown that minor length alterations and side-chain substitutions still result in CXCR5 activation. This observation indicates that the orthosteric pocket of CXCR5 can tolerate these changes without severely affecting the activity. The introduction of bulk on the ligand was well tolerated by the receptor, whereas a loss of contacts was less tolerated. Furthermore, two crystal structures of CXCL13 mutants were solved, both of which represent the first uncomplexed structures of the human protein. These structures were stabilized by unique interactions formed by the N-termini of the ligands, indicating that CXCL13 exhibits substantial N-terminal flexibility while the chemokine core domain remains largely unchanged. Additionally, it was observed that CXCL13 harbors a large degree of flexibility in the C-terminal extension of the ligand. Comparisons with other published structures of human and murine CXCL13 validate the relative rigidity of the core domain as well as the N- and C-terminal mobilities. Collectively, these mutants and their structures provide the field with additional insights into how CXCL13 interacts with CXCR5.

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“…It was recommended that anti-dsDNA-negative SLE, RA and other autoimmune disease patients have significantly increased serum CXCL13 levels compared with healthy controls, although previous studies have never discussed this topic before 9 . It was suggested that CXCL13 plays a key role in the differentiation of B lymphocytes into plasma cells to generate antibodies 6 . However, the disease activity and correlation factors between CXCL13 and RA and other autoimmune diseases should be further studied.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the B-cell-attracting chemokine CXC ligand 13 (CXCL13) is closely related to autoimmune diseases, especially SLE, rheumatoid arthritis (RA), Sjögren's syndrome and other autoimmune diseases [6][7][8][9][10] . CXCL13 is significantly increased in SLE patients, especially in lupus nephritis (LN) patients and is positively correlated with the SLE disease activity index (SLEDAI) and anti-dsDNA titre.…”

Section: Introductionmentioning

confidence: 99%

The CXCL13 chemokine serves as a potential biomarker to diagnose systemic lupus erythaematosus with disease activity

Zeng¹,

Zhang²,

Yuan³

et al. 2020

Preprint

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Objectives: Our study purpose was to assess the regulatory response of the chemokine CXCL13 in the serum of patients with systemic lupus erythaematosus (SLE) and to evaluate its influence on the inflammatory process in SLE. Methods: Serum samples from 97 SLE patients, 49 non-SLE patients (23 patients with other autoimmune diseases and 26 patients with rheumatoid arthritis ) and 50 healthy controls were analysed for the concentration of CXCL13 using ELISA. Results: The results indicated that the serum levels of CXCL13 were significantly higher in SLE patients than in non-SLE patients and healthy controls (p<0.001). Moreover, the level of CXCL13 decreased as the level of anti-dsDNA IgG decreased after treatment between the anti-dsDNA-positive SLE patients and the anti-dsDNA-negative SLE patients. In addition, serum CXCL13 levels were correlated with SLEDAI in different activities of SLE, renal involvement and active LN. Furthermore, the level of CXCL13 was positively related to the SLEDAI,level of anti-dsDNA IgG , level of ESR and RAI of high-avidity IgG ANAs (HA IgG ANAs). Additionally, ROC curve analysis revealed that the serum CXCL13 levels were robust in discriminating patients with active SLE from patients with inactive SLE and SLE patients with high-avidity IgG ANAs from SLE patients with low-avidity IgG ANAs. Conclusions: First, we demonstrated that CXCL13 was elevated in SLE patients regardless of the presence or absence of anti-dsDNA IgG ANAs. Furthermore, HA IgG ANAs might affect the circulation of CXCL13. Therefore, the chemokine CXCL13 might be a risk factor influencing the inflammatory process in SLE.The CXCL13 chemokine serves as a potential biomarker to diagnose systemic lupus erythaematosus with disease activity

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Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis

Cited by 22 publications

References 37 publications

RNA-Seq and Network Analysis Reveal Unique Chemokine Activity Gene Expression Signatures in Synovial Tissue From Rheumatoid Arthritis

RNA-Seq and Network Analysis Reveal Unique Chemokine Activity Gene Expression Signatures in Synovial Tissue From Rheumatoid Arthritis

The N-terminal length and side-chain composition of CXCL13 affect crystallization, structure and functional activity

The CXCL13 chemokine serves as a potential biomarker to diagnose systemic lupus erythaematosus with disease activity

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