Skip to main content
SpringerLink
Log in

Circulating lymphocyte subpopulations in patients with systemic lupus erythematosus and their correlation with disease activity

  • Research
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

The aim of the present study was to evaluate the overall alterations of peripheral blood lymphocyte subsets in patients with systemic lupus erythematosus (SLE). A total of 120 patients diagnosed with SLE and 64 health donors were enrolled. The lymphocyte subsets were detected using flow cytometry. Then the changes of lymphocyte subsets in patients and their correlation with disease activity were investigated. Compared with healthy controls, the counts of lymphocytes, T cells, B cells and NK cells in SLE patients were significantly decreased. Further analysis of T cells subpopulations revealed that the decrease in T cells counts in SLE patients was mainly attributed to a sharp decrease in CD4 + T cells counts. Meanwhile, there was a positive correlation between CD4 + T cells counts and serum complement 3 levels, and patients with lower CD4 + T cells counts had higher SLEDAI score. The counts of CD8 + T cells were comparable between SLE patients and controls, while the proportion of CD8 + T cells and cytotoxic T cells (CD8 + CD28 +) was prominently higher in SLE patients. Besides, the expression of HLA-DR on the surface of T and NK cells was significantly upregulated in SLE patients. Circulating lymphocyte subsets of SLE patients were seriously dysregulated, characterized by a decrease in CD4 + T cells and NK cells, as well as an increase in the proportion of activated T and NK cells. Reduction in CD4 + T cells in SLE patients was highly consistent with disease activity, indicating the crucial role of CD4 + T cells in the onset and progression of SLE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110–21.

    Article  CAS  PubMed  Google Scholar 

  2. Fava A, Petri M. Systemic lupus erythematosus: diagnosis and clinical management. J Autoimmun. 2019;96:1–13.

    Article  PubMed  Google Scholar 

  3. Pons-Estel GJ, Alarcón GS, Scofield L, et al. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010;39(4):257–68.

    Article  PubMed  Google Scholar 

  4. Fayyaz A, Igoe A, Kurien BT, et al. Haematological manifestations of lupus. Lupus Sci Med. 2015;2(1): e000078.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rivero SJ, Díaz-Jouanen E, Alarcón-Segovia D. Lymphopenia in systemic lupus erythematosus. Clinical, diagnostic, and prognostic significance. Arthritis Rheum. 1978;21(3):295–305.

    Article  CAS  PubMed  Google Scholar 

  6. Rakebrandt N, Littringer K, Joller N. Regulatory T cells: balancing protection versus pathology. Swiss Med Wkly. 2016;146: w14343.

    PubMed  Google Scholar 

  7. Ma K, Du W, Wang X, et al. Multiple functions of B cells in the pathogenesis of systemic lupus erythematosus. Int J Mol Sci. 2019;20(23):6021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dema B, Charles N. Advances in mechanisms of systemic lupus erythematosus. Discov Med. 2014;17(95):247–55.

    PubMed  Google Scholar 

  9. Mok CC. Current role of rituximab in systemic lupus erythematosus. Int J Rheum Dis. 2015;18(2):154–63.

    Article  CAS  PubMed  Google Scholar 

  10. Albert D, Dunham J, Khan S, et al. Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis. 2008;67(12):1724–31.

    Article  CAS  PubMed  Google Scholar 

  11. Moulton VR, Tsokos GC. Abnormalities of T cell signaling in systemic lupus erythematosus. Arthritis Res Ther. 2011;13(2):207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Crispín JC, Kyttaris VC, Juang YT, et al. How signaling and gene transcription aberrations dictate the systemic lupus erythematosus T cell phenotype. Trends Immunol. 2008;29(3):110–5.

    Article  PubMed  Google Scholar 

  13. Yang X, Wang W, Xu J, et al. Significant association of CD4(+)CD25(+)Foxp3(+) regulatory T cells with clinical findings in patients with systemic lupus erythematosus. Ann Transl Med. 2019;7(5):93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75(7):1407–15.

    Article  Google Scholar 

  15. Gravano DM, Hoyer KK. Promotion and prevention of autoimmune disease by CD8+ T cells. J Autoimmun. 2013;45:68–79.

    Article  CAS  PubMed  Google Scholar 

  16. Minning S, Xiaofan Y, Anqi X, et al. Imbalance between CD8(+)CD28(+) and CD8(+)CD28(-) T-cell subsets and its clinical significance in patients with systemic lupus erythematosus. Lupus. 2019;28(10):1214–23.

    Article  CAS  PubMed  Google Scholar 

  17. Zahran AM, Abdel-Rahim MH, Elsayh KI, et al. Natural killer and natural killer T cells in juvenile systemic lupus erythematosus: relation to disease activity and progression. Arch Immunol Ther Exp (Warsz). 2019;67(3):161–9.

    Article  CAS  PubMed  Google Scholar 

  18. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Li C, Mu R, Lu XY, et al. Antilymphocyte antibodies in systemic lupus erythematosus: association with disease activity and lymphopenia. J Immunol Res. 2014;2014: 672126.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wofsy D, Seaman WE. Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal antibody to L3T4. J Immunol. 1987;138(10):3247–53.

    Article  CAS  PubMed  Google Scholar 

  21. Rivero SJ, Llorente L, Díaz-Jouanen E, et al. T-lymphocyte subpopulation in untreated SLE. Variat Dis Act Arthritis Rheum. 1977;20(6):1169–73.

    Article  CAS  Google Scholar 

  22. Tran DQ, Ramsey H, Shevach EM. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood. 2007;110(8):2983–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lyssuk EY, Torgashina AV, Soloviev SK, et al. Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus. Adv Exp Med Biol. 2007;601:113–9.

    Article  PubMed  Google Scholar 

  24. Alvarado-Sánchez B, Hernández-Castro B, Portales-Pérez D, et al. Regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun. 2006;27(2):110–8.

    Article  PubMed  Google Scholar 

  25. Zhang B, Zhang X, Tang FL, et al. Clinical significance of increased CD4+CD25-Foxp3+ T cells in patients with new-onset systemic lupus erythematosus. Ann Rheum Dis. 2008;67(7):1037–40.

    Article  CAS  PubMed  Google Scholar 

  26. Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol. 2002;2(2):116–26.

    Article  CAS  PubMed  Google Scholar 

  27. Fernández-Grande E, Cabrera CM, González B, et al. Enhanced HLA-DR expression on T-lymphocytes from patients in early stages of non-surgical sepsis. Med Clin (Barc). 2019;152(9):346–9.

    Article  PubMed  Google Scholar 

  28. Zhou H, Hu B, Huang N, et al. Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus. Clin Rheumatol. 2018;37(9):2405–13.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

I would like to thank Dr. Yu for her valuable assistance and all of the staff members of the Clinical Laboratory Centre. And I shall extend my thanks to my teacher Professor Jun He, who has helped me develop the fundamental and essential academic competence.

Funding

The authors have no funding to report.

Author information

Authors and Affiliations

  1. Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, 266000, Shandong, People’s Republic of China

    Zhiluo Yang & Yi Lu

  2. Nantong Rich Hospital, The Fourth Affiliated Hospital of Yangzhou University, Nantong, 226010, Jiangsu, People’s Republic of China

    Zhiluo Yang

  3. The Affiliated Hospital of Qingdao University, Qingdao, 266555, Shandong, People’s Republic of China

    Wei Yu

Authors
  1. Zhiluo Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZY and YL designed the project. ZY and WY conducted the experiment and analyzed the data. ZY drafted the manuscript and YL helped to revise the paper. YL approved the final version to be published. All the authors agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Yi Lu.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Qingdao Municipal Hospital Group, and the research was carried out in accordance with the World Medical Association Declaration of Helsinki. Written informed consents were obtained from all participants included in the study.

Consent for publication

Written informed consent was obtained from the patient for publication of this research article and any accompanying images.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 15 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, Z., Yu, W. & Lu, Y. Circulating lymphocyte subpopulations in patients with systemic lupus erythematosus and their correlation with disease activity. Clin Exp Med 23, 4757–4763 (2023). https://doi.org/10.1007/s10238-023-01237-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-023-01237-4

Keywords

Search

Navigation