Abstract
Objectives
CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA.
Methods
All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019). According to random effects model, standardized mean difference (SMD) and 95% confidence interval (CI) of CXCL13 levels in SLE and RA were calculated by Stata 12.0 software.
Results
Totally, 15 studies were selected (981 SLE patients and 380 healthy controls, 332 RA patients and 147 healthy controls). SLE and RA patients were significantly increased in circulating CXCL13 levels (SMD = 1.851, 95% CI 0.604–3.098; SMD = 1.801, 95% CI = 1.145–2.457). Subgroup analyses showed that SLE patients from the Chinese group and systemic lupus erythematosus disease activity index (SLEDAI) score ≥ 6 group had higher circulating CXCL13 levels (SMD = 2.182, 95% CI 0.135–4.229; SMD = 0.767, 95% CI 0.503–1.030). However, there were no significant changes in CXCL13 concentrations in SLE patients from the English and SLEDAI score < 6 group. Similarly, subgroup analyses presented that RA patients from different classifications showed higher circulating CXCL13 levels. There was no publication bias.
Conclusions
This meta-analysis demonstrated increased circulating CXCL13 concentrations in SLE and RA patients. Circulating CXCL13 levels may act as biomarkers and therapy targets in the diagnosis and treatment of SLE and RA.
Key Point • First, CXC ligand 13 (CXCL13) is closely related to the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), Second, this study may provide novel therapeutic targets for the treatment of SLE and RA patients. This meta-analysis provides a comprehensive analysis of circulating CXCL13 levels in patients with SLE and RA and also explores related influencing factors. |
Similar content being viewed by others
References
Coronel-Restrepo N, Posso-Osorio I, Naranjo-Escobar J, Tobón GJ (2017) Autoimmune diseases and their relation with immunological, neurological and endocrinological axes. Autoimmun Rev 16(7):684–692. https://doi.org/10.1016/j.autrev.2017.05.002
Agmon-Levin N, Blank M, Paz Z, Shoenfeld Y (2009) Molecular mimicry in systemic lupus erythematosus. Lupus 18(13):1181–1185. https://doi.org/10.1177/0961203309346653
D’Cruz DP, Khamashta MA, Hughes GR (2007) Systemic lupus erythematosus. Lancet 369(9561):587–596
Chinses Society of rheumatology (2003) Guidelines for the diagnosis and treatment of systemic lupus erythematosus. Chin J Rheumatol 7(8):508–513
Fortuna G, Brennan MT (2013) Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. Dent Clin N Am 57(4):631–655. https://doi.org/10.1016/j.cden.2013.06.003
Smolen JS, Aletaha D, McInnes IB (2016) Rheumatoid arthritis. Lancet 388(10055):2023–2038. https://doi.org/10.1016/s0140-6736(16)30173-8
Shi K, Hayashida K, Kaneko M, Hashimoto J, Tomita T, Lipsky PE, Yoshikawa H, Ochi T (2001) Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients. J Immunol 166(1):650–655. https://doi.org/10.4049/jimmunol.166.1.650
Zhang X, Yang CX (2016) Research progress of CXCL-13 antibody in the treatment of autoimmune disease. Pract Pharm Clin Remed 19(8):1046–1049. https://doi.org/10.14053/j.cnki.ppcr.201608032
Schiffer L, Worthmann K, Haller H, Schiffer M (2015) CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis from bench to bedside? Clin Exp Immunol 179(1):85–89. https://doi.org/10.1111/cei.12439
Li LL (2016) Studies on the relationship between CXCL13 and systemic lupus erythematosus. J Nantong Univ (Med Sci) 36(4):287–290. https://doi.org/10.16424/j.cnki.cn32-1087/r.2016.04.013
Worthmann K, Gueler F, von Vietinghoff S, Davalos-Mißlitz A, Wiehler F, Davidson A, Witte T, Haller H, Schiffer M, Falk CS, Schiffer L (2014) Pathogenetic role of glomerular CXCL13 expression in lupus nephritis. Clin Exp Immunol 178(1):20–27. https://doi.org/10.1111/cei.12380
Luo DH, Wan X, Liu JM, Tong TJ (2017) How to estimate he sample mean and standard deviation from the sample size, median, extremes or quartiles. Chin J Evid Based Med 17(11):1350–1355
Schiffer L, Kümpers P, Davalos-Misslitz AM, Haubitz M, Haller H, Anders HJ, Witte T, Schiffer M (2009) B-cell-attracting chemokine CXCL13 as a marker of disease activity and renal involvement in systemic lupus erythematosus(SLE). Nephrol Dial Transplant 24(12):3708–3712. https://doi.org/10.1093/ndt/gfp343
Lee HT, Shiao YM, Wu TH, Chen WS, Hsu YH, Tsai SF, Tsai CY (2010) Serum BLC/CXCL13 concentrations and renal expression of CXCL13/CXCR5 in patients with systemic lupus erythematosus and lupus nephritis. J Rheumatol 37(1):45–52. https://doi.org/10.3899/jrheum.090450
Wong CK, Wong PT, Tam LS, Li EK, Chen DP, Lam CW (2010) Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity. J Clin Immunol 30(1):45–52. https://doi.org/10.1007/s10875-009-9325-5
Schiffer L, Kielstein JT, Haubitz M, Lührs H, Witte T, Haller H, Kümpers P, Schiffer M (2011) Elevation of serum CXCL13 in SLE as well as in sepsis. Lupus 20(5):507–511. https://doi.org/10.1177/0961203310383301
Run YM, Rao H, Jiang H, Zhu YF, Cao H, Wang JM (2015) Detection of serum chemokine CXCL family contents in patients with systemic lupus erythematosus and its clinical significance. J Hainan Med Univ 21(12):1733–1736. https://doi.org/10.13210/j.cnki.jhmu.20150827.006
Xie WY, Nie LP, Yang YH (2015) The study of circulating CXCL13 level and expression of its receptor CXCR5 with system lupus erythematosus. Chin J Lab Diagn 19(10):1689–1692.6
Dong DQ, Zhang JM, Li HY, Sun WK (2016) Expressions of CXCR5 mRNA and CXCL13 mRNA in patients with systemic lupus erythematosus. Chin J Clinic (Electronic Edition) 10(18):2700–2704. https://doi.org/10.3877/cma.j.issn.1674-0785.2016.18.005
Fang C, Luo T, Lin L (2017) The correlational research among serum CXCL13 levels, circulating plasmablasts and memory B cells in patients with systemic lupus erythematosus: a STROBE-compliant article. Medicine(Baltimore) 96(48):e8675. https://doi.org/10.1097/MD.0000000000008675
He DN, Hu JK, Zhu JR, Dai SH, Liu YW, Hu N (2018) Serum CXCL13 and renal involvement in lupusc nephritis. Jiangxi Med J 53(8):822–824+833. https://doi.org/10.3969/j.issn.1006-2238.2018.8.012
Rioja I, Hughes FJ, Sharp CH, Warnock LC, Montgomery DS, Akil M, Wilson AG, Binks MH, Dickson MC (2008) Potential novel biomarkers of disease activity in rheumatoid arthritis patients: CXCL13, CCL23, transforming growth factor alpha, tumor necrosis factor receptor superfamily member 9, and macrophage colony-stimulating factor. Arthritis Rheum 58(8):2257–2267. https://doi.org/10.1002/art.23667
Ahmed SF, Badr T, Hosny SM, Hamayed HFA (2013) Assessment of synovitis in early rheumatoid arthritis by CXCL13 serum levels and power Doppler ultrasonography: correlation with disease activity. Egypt Rheumatologist 35(1):21–27. https://doi.org/10.1016/j.ejr.2012.09.001
Sherif NM, Arafa MM, Ibrahim SE, Moussa SG (2013) CXC ligand 13 in rheumatoid arthritis and its relation to secondary Sjögren’s syndrome. Egypt Rheumatologist 35(3):121–126. https://doi.org/10.1016/j.ejr.2013.03.004
Zhang MM, Zhang R, Xu JH (2013) Study of serum IL32 and chemokine CXCL13 in patients with rheumatoid arthritis. Acta Univ Med Anhui 48(12):1512–1515. https://doi.org/10.19405/j.cnki.issn1000-1492.2013.12.024
An LM, Chu TS, Liu W, Liu B, Zhu Q (2018) Expression and significance of serum CXCL13 in rheumatoid arthritis. J Chin Pract Diagn 32(3):248–250. https://doi.org/10.13507/j.issn.1674-3474.2018.03.012
Allam SI, Sallam RA, Elghannam DM, El-Ghaweet AI (2019) Clinical significance of serum B cell chemokine (CXCL13) in early rheumatoid arthritis patients. Egypt Rheumatologist 41(1):11–14. https://doi.org/10.1016/j.ejr.2018.04.003
Worthmann K, Gueler F, von Vietinghoff S, Davalos-MiBlitz A, Wiehler F, Davidson A, Witte T, Haller H, Schiffer M, Falk CS, Schiffer L (2014) Pathogenetic role of glomerular CXCL13 expression in lupus nephritis. Clin Exp Immunol 178(1):20–27. https://doi.org/10.1111/cei.12380
Oglesby A, Shaul AJ, Pokora T, Paramore C, Cragin L, Dennis G, Narayanan S, Weinstein A (2013) Adverse event burden, resource use, and costs associated with immunosuppressant medications for the treatment of systemic lupus erythematosus: a systematic literature review. Int J Rheumatol:347520. https://doi.org/10.1155/2013/347520
Latek D, Modzelewska A, Trzaskowski B, Palczewski K, Filipek S (2012) G protein-coupled receptors--recent advances. Acta Biochim Pol 59(4):515–529
Ishikawa S, Sato T, Abe M, Nagai S, Onai N, Yoneyama H, Zhang Y, Suzuki T, Hashimoto S, Shirai T, Lipp M, Matsushima K (2001) Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) by C11b+CD11c+ dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC. J Exp Med 193(12):1393–1402
Wu X, Guo J, Ding R, Lv B, Bi L (2015) CXCL13 blockade attenuates lupus nephritis of MRL/lpr mice. Acta Histochem 117(8):732–737. https://doi.org/10.1016/j.acthis.2015.09.001
Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350(25):2572–2581
Jones JD, Hamilton BJ, Challener GJ, de Brum-Fernandes AJ, Cossette P, Liang P, Masetto A, Ménard HA, Carrier N, Boyle DL, Rosengren S, Boire G, Rigby WF (2014) Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels. Arthritis Res Ther 16(2):R103. https://doi.org/10.1186/ar4552
Bugatti S, Manzo A, Benaglio F, Klersy C, Vitolo B, Todoerti M, Sakellariou G, Montecucco C, Caporali R (2012) Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs. Arthritis Res Ther 14(1):R34. https://doi.org/10.1186/ar3742
Bugatti S, Manzo A, Vitolo B, Benaglio F, Binda E, Scarabelli M, Humby F, Caporali R, Pitzalis C, Montecucco C (2014) High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease. Rheumatology (Oxford) 53(10):1886–1895. https://doi.org/10.1093/rheumatology/keu163
Rosengren S, Wei N, Kalunian KC, Kavanaugh A, Boyle DL (2011) CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis. Rheumatology(Oxford) 50(3):603–610. https://doi.org/10.1093/rheumatology/keq337
Shapira Y, Agmon-Levin N, Shoenfeld Y (2010) Geoepidemiology of autoimmune rheumatic diseases. Nat Rev Rheumatol 6(8):468–476. https://doi.org/10.1038/nrrheum.2010.86
Wang JB, Pan HF, Ye DQ (2018) Association of lnc5150 gene polymorphisms with systemic lupus erythematosus. Chin J Dis Control Prev 22(9):929–932. https://doi.org/10.16462/j.cnki.zhjbkz.2018.09.014
Huang LL, Xu JH, Xu SQ, Xiao H, Chang L, Liu N, Ma Q (2016) Treat-to-target of rheumatoid arthritis and potential determinants. Chin J Dis Control Prev 20(6):586–589. https://doi.org/10.16462/j.cnki.zhjbkz.2016.06.012
Han JH, Suh CH, Jung JY, Nam JY, Kwon JE, Yim H, Kim HA (2015) Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation in active adult-onset still’s disease. Arthritis Res Ther 17:260. https://doi.org/10.1186/s13075-015-0773-4
Acknowledgments
Thanks to the selfless help of the lab teachers and classmates.
Funding
This meta-analysis was funded by the Chinese national high level personnel special support plan.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Disclosures
None.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bao, YQ., Wang, JP., Dai, ZW. et al. Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Clin Rheumatol 39, 281–290 (2020). https://doi.org/10.1007/s10067-019-04775-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-019-04775-z