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Immune profile alterations of systemic lupus erythematosus patients with infections

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Abstract

This study aimed to elucidate the immune status of systemic lupus erythematosus (SLE) patients with infections. We enrolled 253 SLE patients including 77 patients with infections. Clinical features and immunological parameters were analyzed, with particular reference to neutrophil CD64 (nCD64) expression, myeloid-derived suppressor cells (MDSCs), activated T cells and multiple cytokines. Among the 77 SLE patients with infections, 32 patients (41.56%) developed fever and 20 patients (25.97%) developed serositis, which were higher compared to the non-infection group. A considerably higher level of nCD64 was found in the infection group (4.65 vs 1.01, P < 0.001). In addition, the infection group exhibited higher percentages of total MDSCs (6.99 vs 4.30%, P = 0.003), polymorphonuclear MDSCs (PMN-MDSCs) (P = 0.032) and monocytic MDSCs (M-MDSCs) (P = 0.015). T cells were more activated during infections, with an elevated level of IL-2R (P < 0.001). Specifically, higher percentages of CD4+CD38+ T cells (55.73 vs 50.17%, P = 0.036), CD8+HLA-DR+ T cells (59.82 vs 47.99%, P < 0.001) and CD8+CD38+ T cells (68.59 vs 63.90%, P = 0.044) were identified in the infection group. Furthermore, the serum levels of IL-6, IL-8 and IL-10 were elevated in the infection group (all P < 0.001). Higher proportions of neutrophils, CD4+ and CD8+ T cells, and MDSCs were activated during infections in SLE patients. Additionally, the serum cytokines altered during infections, with noticeably elevated levels of IL-6, IL-8 and IL-10. Infections may lead to the amplification of immune alterations in SLE.

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Data availability

The data used during the study are available on reasonable request.

References

  1. Tsokos GC. Autoimmunity and organ damage in systemic lupus erythematosus. Nat Immunol. 2020;21(6):605–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Crow MK. Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets. Ann Rheum Dis. 2023.

  3. Kaul A, Gordon C, Crow MK, et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2:16039.

    Article  PubMed  Google Scholar 

  4. He J, Li Z. Dilemma of immunosuppression and infection risk in systemic lupus erythematosus. Rheumatology (Oxford). 2023;62(Suppl 1):i22–9.

    Article  CAS  PubMed  Google Scholar 

  5. Dörner T, Furie R. Novel paradigms in systemic lupus erythematosus. Lancet. 2019;393(10188):2344–58.

    Article  PubMed  Google Scholar 

  6. Goldblatt F, Chambers S, Rahman A, Isenberg DA. Serious infections in British patients with systemic lupus erythematosus: hospitalisations and mortality. Lupus. 2009;18(8):682–9.

    Article  CAS  PubMed  Google Scholar 

  7. Dias AMB, do Couto MCM, Duarte CCM, Inês LPB, Malcata AB. White blood cell count abnormalities and infections in one-year follow-up of 124 patients with SLE. Ann N Y Acad Sci. 2009;1173:103–7.

    Article  PubMed  Google Scholar 

  8. Goldblatt F, Yuste J, Isenberg DA, Rahman A, Brown J. Impaired C3b/iC3b deposition on Streptococcus pneumoniae in serum from patients with systemic lupus erythematosus. Rheumatology (Oxford). 2009;48(12):1498–501.

    Article  CAS  PubMed  Google Scholar 

  9. Paton NI, Cheong IK, Kong NC, Segasothy M. Risk factors for infection in Malaysian patients with systemic lupus erythematosus. QJM. 1996;89(7):531–8.

    Article  CAS  PubMed  Google Scholar 

  10. Noël V, Lortholary O, Casassus P, et al. Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus. Ann Rheum Dis. 2001;60(12):1141–4.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ruiz-Irastorza G, Olivares N, Ruiz-Arruza I, Martinez-Berriotxoa A, Egurbide M-V, Aguirre C. Predictors of major infections in systemic lupus erythematosus. Arthritis Res Ther. 2009;11(4):R109.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 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  PubMed  Google Scholar 

  13. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813–21.

    Article  PubMed  Google Scholar 

  14. Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020;71(6):1367–76.

    Article  PubMed  Google Scholar 

  15. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288–91.

    PubMed  Google Scholar 

  16. Olivares-Zavaleta N, Carmody A, Messer R, Whitmire WM, Caldwell HD. Chlamydia pneumoniae inhibits activated human T lymphocyte proliferation by the induction of apoptotic and pyroptotic pathways. J Immunol. 2011;186(12):7120–6.

    Article  CAS  PubMed  Google Scholar 

  17. Poujol F, Monneret G, Pachot A, Textoris J, Venet F. Altered T lymphocyte proliferation upon lipopolysaccharide challenge ex vivo. PLoS ONE. 2015;10(12): e0144375.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Merayo-Chalico J, Gómez-Martín D, Piñeirúa-Menéndez A, Santana-De Anda K, Alcocer-Varela J. Lymphopenia as risk factor for development of severe infections in patients with systemic lupus erythematosus: a case-control study. QJM. 2013;106(5):451–7.

    Article  CAS  PubMed  Google Scholar 

  19. Repp R, Valerius T, Sendler A, et al. Neutrophils express the high affinity receptor for IgG (Fc gamma RI, CD64) after in vivo application of recombinant human granulocyte colony-stimulating factor. Blood. 1991;78(4):885–9.

    Article  CAS  PubMed  Google Scholar 

  20. Davis BH, Olsen SH, Ahmad E, Bigelow NC. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Arch Pathol Lab Med. 2006;130(5):654–61.

    Article  CAS  PubMed  Google Scholar 

  21. Yeh C-F, Wu C-C, Liu S-H, Chen K-F. Comparison of the accuracy of neutrophil CD64, procalcitonin, and C-reactive protein for sepsis identification: a systematic review and meta-analysis. Ann Intensive Care. 2019;9(1):5.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Cid J, Aguinaco R, Sánchez R, García-Pardo G, Llorente A. Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis. J Infect. 2010;60(5):313–9.

    Article  PubMed  Google Scholar 

  23. Burn GL, Foti A, Marsman G, Patel DF, Zychlinsky A. The neutrophil. Immunity. 2021;54(7):1377–91.

    Article  CAS  PubMed  Google Scholar 

  24. Rahman S, Sagar D, Hanna RN, et al. Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus. Ann Rheum Dis. 2019;78(7):957–66.

    Article  CAS  PubMed  Google Scholar 

  25. Florez-Pollack S, Tseng L-C, Kobayashi M, Hosler GA, Ariizumi K, Chong BF. Expansion of myeloid-derived suppressor cells in the peripheral blood and Lesional skin of cutaneous lupus patients. J Invest Dermatol. 2019;139(2):478–81.

    Article  CAS  PubMed  Google Scholar 

  26. Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021;21(8):485–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hollen MK, Stortz JA, Darden D, et al. Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis. Crit Care. 2019;23(1):355.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mathias B, Delmas AL, Ozrazgat-Baslanti T, et al. Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg. 2017;265(4):827–34.

    Article  PubMed  Google Scholar 

  29. Katsuyama E, Suarez-Fueyo A, Bradley SJ, et al. The CD38/NAD/SIRTUIN1/EZH2 axis mitigates cytotoxic CD8 T cell function and identifies patients with SLE prone to infections. Cell Rep. 2020;30(1):112-123.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li Z, Yang Z, Hu P, et al. Cytokine expression of lung bacterial infection in newly diagnosed adult hematological malignancies. Front Immunol. 2021;12: 748585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nat Rev Rheumatol. 2017;13(7):399–409.

    Article  CAS  PubMed  Google Scholar 

  32. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448–57.

    Article  CAS  PubMed  Google Scholar 

  33. Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med. 2021;53(7):1116–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang J, Hooper WC, Phillips DJ, Talkington DF. Cytokines in Mycoplasma pneumoniae infections. Cytokine Growth Factor Rev. 2004;15(2–3):157–68.

    Article  CAS  PubMed  Google Scholar 

  35. Ouyang W, O’Garra A. IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity. 2019;50(4):871–91.

    Article  CAS  PubMed  Google Scholar 

  36. Preble OT, Black RJ, Friedman RM, Klippel JH, Vilcek J. Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science. 1982;216(4544):429–31.

    Article  CAS  PubMed  Google Scholar 

  37. Mathian A, Mouries-Martin S, Dorgham K, et al. Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse. Ann Rheum Dis. 2019;78(12):1669–76.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are very grateful to Dr Shi Bisheng and Dr Ma Xiaowei from Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University for flow cytometry analysis. We thank the patients and their families for their cooperation.

Funding

This work was supported by the National Natural Science Foundation of China (82001707 and 81373209), Shanghai Sailing Program (22YF1424000 and 20YF1425700), and the Fundamental Research Funds for the Central Universities (YG2023ZD09).

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Contributions

All authors contributed to the study conception and design. RG and LL designed the study and revised the manuscript. LZ and LG drafted the manuscript. LT and XL collected and analysed clinical data. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Liangjing Lu or Ruru Guo.

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The authors declare that they have no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

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Written informed consent for publication of the study was obtained from all individual participants included in the study. All authors approved the final manuscript.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Renji Hospital (Number: [2017]201), Shanghai, China.

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Zhi, L., Gu, L., Tong, L. et al. Immune profile alterations of systemic lupus erythematosus patients with infections. Clin Exp Med 23, 4765–4777 (2023). https://doi.org/10.1007/s10238-023-01220-z

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