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

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Abstract

The aim of our study was to assess the regulatory response of the chemokine CXCL13 in the serum of systemic lupus erythematosus (SLE) patients with disease activity and to evaluate its influence on the inflammatory process in SLE. 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 analyzed for the concentration of CXCL13 using ELISA. 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, statically analysis revealed that CXCL13 would be a best diagnostic value for determining the disease activity of SLE due to its moderate sensitivity (93.5%), specificity (95%), PPV (98.6%), NPV (79.2%) and OR(95%CI,250(30.303–1000)), at a cut-off level of 15.27 pg/mL. First, we indicated 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.

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Some or all data, models or code generated or used during the study are available from the corresponding author by request.

References

  1. Hargraves MM, Richmond H, Morton R. Presentation of two bone marrow elements the tart cell and the L.E. cell. Proc Staff Meet Mayo Clinic. 1948;23(2):25–8.

    CAS  Google Scholar 

  2. Rosken GHJ, van Beek AA, Bakker-Jonges LE, Schreurs MWJ. Antinuclear antibodies in systemic autoimmune disease. Ned Tijdschr Geneeskd 2020, 164.

  3. Oliveira RC, Oliveira IS, Santiago MB, Sousa Atta ML, Atta AM. High avidity dsDNA Autoantibodies in Brazilian women with systemic lupus erythematosus: correlation with active disease and renal dysfunction. J Immunol Res. 2015. https://doi.org/10.1155/2015/814748.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kim HA, Jeon JY, Choi GS, et al. The antichromatin antibodies can be useful as a diagnostic tool and disease activity marker of systemic lupus erythematosus in Koreans. Clin Immunol. 2008;128(2):277–83.

    Article  CAS  Google Scholar 

  5. Fritzler MJ, Salazar M. Diversity and origin of rheumatologic autoantibodies. Clin Microbiol Rev. 1991;4(3):256–69.

    Article  CAS  Google Scholar 

  6. Bao YQ, Wang JP, Dai ZW, et al. Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Clin Rheumatol. 2020;39(1):281–90.

    Article  Google Scholar 

  7. Niederkorn A, Fruhauf J, Schwantzer G, et al. CXCL13 is an activity marker for systemic, but not cutaneous lupus erythematosus: a longitudinal cohort study. Arch Dermatol Res. 2018;310(6):485–93.

    Article  CAS  Google Scholar 

  8. Lee HT, Shiao YM, Wu TH, et al. Serum BLC/CXCL13 concentrations and renal expression of CXCL13/CXCR5 in patients with systemic lupus erythematosus and lupus Nephritis. J Rheumatol. 2010;37(1):45–52.

    Article  CAS  Google Scholar 

  9. Schiffer L, Kümpers P, Davalos-Misslitz AM, et al. B-cell-attracting chemokine CXCL13 as a marker of disease activity and renal involvement in systemic lupus erythematosus (SLE). Nephrol Dial Transplant. 2009;24(12):3708–12.

    Article  CAS  Google Scholar 

  10. Barone F, Bombardieri M, Rosado MM, et al. CXCL13, CCL21, and CXCL12 expression in salivary glands of patients with Sjogren’s syndrome and MALT lymphoma: association with reactive and malignant areas of lymphoid organization. J Immunol. 2008;180(7):5130–40.

    Article  CAS  Google Scholar 

  11. Aringer M, Costenbader K, Daikh D, et al. 2019 European league against rheumatism/American college of rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151–9.

    Article  Google Scholar 

  12. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35(6):630–40.

    Article  CAS  Google Scholar 

  13. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

    Article  CAS  Google Scholar 

  14. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271–7.

    Article  CAS  Google Scholar 

  15. Gordon C, Jayne D, Pusey C, et al. European consensus statement on the terminology used in the management of lupus glomerulonephritis. Lupus. 2009;18(3):257–63.

    Article  CAS  Google Scholar 

  16. Zeng Y, Lin Y, Wang X, et al. Assessment of a high-avidity IgG ANAs for the diagnosis and activity prediction of systemic lupus erythematosus. Clin Rheumatol. 2020;39:2619–29.

    Article  Google Scholar 

  17. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American college of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81.

    Article  Google Scholar 

  18. Zeng Y-L, Lin Y-Q, Zhang N-N, et al. CXCL13 chemokine as a promising biomarker to diagnose neurosyphilis in HIV-negative patients. Springerplus. 2016;5:743–51.

    Article  Google Scholar 

  19. Yanli Zeng YZ, Chen Qinggui, Huang Qinghe, Lin Yiqiang, Wang Xuelian, Wang Jiajia, Jiang Longcan, Xiao Yun. Distribution of IgG subclass anti-nuclear antibodies (ANAs) in systemic lupus erythematosus. Lupus. 2021. https://doi.org/10.1177/0961203321995242.

    Article  PubMed  Google Scholar 

  20. Rioja I, Hughes FJ, Sharp CH, et al. 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. 2008;58(8):2257–67.

    Article  CAS  Google Scholar 

  21. Wong CK, Wong PT, Tam LS, Li EK, Chen DP, Lam CW. Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity. J Clin Immunol. 2010;30(1):45–52.

    Article  CAS  Google Scholar 

  22. Ishikawa S, Nagai S, Sato T, et al. Increased circulating CD11b+CD11c+ dendritic cells (DC) in aged BWF1 mice which can be matured by TNF-alpha into BLC/CXCL13-producing DC. Eur J Immunol. 2002;32(7):1881–7.

    Article  CAS  Google Scholar 

  23. Schiffer L, Kielstein JT, Haubitz M, et al. Elevation of serum CXCL13 in SLE as well as in sepsis. Lupus. 2011;20(5):507–11.

    Article  CAS  Google Scholar 

  24. Kulkarni O, Anders HJ. Chemokines in lupus nephritis. Front Biosci. 2008;13:3312–20.

    Article  CAS  Google Scholar 

  25. Moreth K, Brodbeck R, Babelova A, et al. The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis. J Clin Invest. 2010;120(12):4251–72.

    Article  CAS  Google Scholar 

  26. Greisen SR, Schelde KK, Rasmussen TK, et al. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic “window of opportunity.” Arthritis Res Ther. 2014;16(5):434–43.

    Article  Google Scholar 

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Acknowledgments

This work was supported by the Natural Science Foundation of Fujian Province (2017J01378).

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Authors and Affiliations

Authors

Contributions

Conceived and designed the experiments: Y-LZ, YZ, Y-Q L. Performed the experiments: X-L W, Q-G C, Q-H H. Analyzed the data: Y-LZ, YX. Contributed reagents/materials/analysis tools: J-J W,L-C J. Wrote the paper: YX, Y-LZ. Revised the manuscript critically for important intellectual content: Y-LZ. All authors read and approved the final manuscript.

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Correspondence to Yun Xiao.

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The authors report no conflicts of interest.

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The study was approved by the Institutional Ethics Committee of Zhongshan Hospital, Medical College Xiamen University and conforms to the ethical guidelines of the Declaration of HELSINKI. Requirement for individual patient consent forms was waived due to the retrospective, observational nature of the study.

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Zeng, Y., Zhang, Y., Lin, Y. et al. The CXCL13 chemokine serves as a potential biomarker to diagnose systemic lupus erythematosus with disease activity. Clin Exp Med 21, 611–619 (2021). https://doi.org/10.1007/s10238-021-00707-x

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  • DOI: https://doi.org/10.1007/s10238-021-00707-x

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