Regulatory T cells and Disease damage in systemic lupus erythematosus

Document Type : Original Article

Authors

1 Clinical Pathology department, Faculty of Medicine, Helwan University, Cairo, Egypt.

2 Clinical Pathology department, Faculty of Medicine, Cairo University, Cairo, Egypt.

3 Rheumatology and Rehabilitation department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Abstract

Background: Systemic lupus erythematosus (SLE) is an inflammatory, multisystem autoimmune disorder characterized by a multitude of autoantibody production and immune complex deposition, causing damage to multiple organs. Dysfunction of T and B cells are believed to be essential factors involved in the disease pathogenesis. A lack or defect in Treg function is generally considered to support SLE pathology. Aim: Our study aimed to assess CD4+ CD25+ Foxp3+ T regulatory cellspercentage in SLE patients and its relation to activity index and damage index. Methods: 50 SLE patients and 50 controls were enrolled in the study. Flowcytometric determination of peripheral Treg cells was done for all participants. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI -2k) while disease damage was measured using the Systemic Lupus international collaborating clinics American College of Rheumatology Damage Index (SLICC/ACR DI) which were correlated with T regulatory cells percentage in cases only. Results: Treg cells percentage was significantly decreased in SLE patients when compared with healthy controls (0.1% to 0.9% vs 0.9% to 2.1%) (p< 0.001).As regard SLEDAI -2k, there was a negative correlation between Treg cells percentile and SLEDAI-2k (p< 0.001). Also there was a negative correlation between Treg cells percentile and damage index (SLICC/ACR DI) (p< 0.001). Regarding the correlation between SLEDAI -2K with damage index (SLICC/ACR DI), we found highly significant positive correlation (p< 0.001). Conclusion: Our study showed that Tregs percentile were significantly lower in SLE patients when compared with healthy controls.Treg cells % have significant association with SLEDAI and damage index suggesting the value of Tregs as activity biomarker and marker of damage. 

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References

  1. Bruce IN, O'Keeffe AG, Farewell V, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort Annals of the Rheumatic Diseases 2015; 74:1706-1713.
  2. Buckner JH. Mechanisms of impaired regulation by CD4+CD25+ FOXP3+ regulatory T cells in human autoimmune diseases. Nature Reviews Immunology. 2010; 10: 849–859.
  3. Ma L, Zhao P, Jiang Z, Shan Y and Jiang Y. Imbalance of different types of CD4+forkhead box protein 3 (FoxP3) + T cells in patients with new-onset systemic lupus erythematosus. ClinExpImmunol 2013; 174:345–55.
  4. Sharma R and Kinsey GR. Regulatory T Cells in Acute and Chronic Kidney Diseases. Am. J. Physiol. Renal Physiol 2018; 314: 679–698.
  5. Chang X, Zheng P and Liu Y. FoxP3: a genetic link between immunodeficiency and autoimmune diseases. Autoimmun Rev 2006; 5:399–402.
  6. Josefowicz SZ, Lu LF and Rudensky AY. Regulatory T cells: mechanisms of differentiation and function, Annu Rev Immunol 2012; 30: 531–564.
  7. Banham AH. Cell-surface IL-7 receptor expression facilitates the purification of FOXP3 (+) regulatory T cells. Trends Immunol 2006; 27:541–4.
  8. Bluestone JA, Tang Q and Sedwick CE.T regulatory cells in autoimmune diabetes: Past challenges, future prospects J ClinImmunol 2008; 28:677-684.
  9. Nuttall A and Isenberg DA. Assessment of disease activity, damage and quality of life in systemic lupus erythematosus: new aspects. Best Pract Res ClinRheumatol 2013; 27(3):309-318.
  10. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT and Fortin PR. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. ArthritisRheum 2012; 64:2677–2686.
  11. Gladman DD, Ibañez D and Urowitz MB. Systemic lupus erythematosus disease activity index 2000, J Rheumatol 2002; 29:288-291.
  12. Gladman D, Ginzler E, Goldsmith C, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39:363–369.
  13. Aringer M, Costenbader K, Daikh D, et al., European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019; 78:1151–1159.
  14. Cai XY, Luo M, Lin XJ et al. Expression and significance of Th17 and Treg cells in peripheral blood of patients with systemic lupus erythematosus. Zhonghua Yi XueZaZhi 2012; 92:460–463.
  15. Habibagahi M, Habibagahi Z, Jaberipour M et al. Quantification of regulatory T cells in peripheral blood of patients with systemic lupus erythematosus. RheumatolInt 2011; 31:1219–1225.
  16. Henriques A, Ines L, Couto M et al. Frequency and functional activity of Th17, Tc17 and other T-cell subsets in systemic lupus erythematosus. Cell Immunol 2010; 264:97–103.
  17. Ma L, Zhao P, Jiang Z et al. Imbalance of different types of CD4+ forkhead box protein 3 (FoxP3) + T cells in patients with new-onset systemic lupus erythematosus. ClinExpImmunol 2013; 174:345–355.
  18. Xing Q, Wang B, Su H et al., Elevated Th17 cells are accompanied by FoxP3? Treg cells decrease in patients with lupus nephritis. RheumatolInt, 2012; 32:949–958.
  19. Costa N, Marques O, Godinho SI, Carvalho C, Leal B and Figueiredo AM. Two separate effects contribute to regulatory T cell defect in systemic lupus erythematosus patients and their unaffected relatives. ClinExpImmunol 2017; 189:318–330.
  20. Yates J, Whittington A, Mitchell P, Lechler R, Lightstone L and Lombardi G. Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis. ClinExpImmunol 2008; 153:44–55.
  21. Azab N, Bassyouni I, Emad Y, Abd El-Wahab G, Hamdy G and Mashahit M. CD4 +CD25+regulatory T cells (TREG) in systemic lupus erythematosus (SLE) patients: the possible influence of treatment with corticosteroids. ClinImmunol 2008; 127:151–157.
  22. Yan B, Ye S, Chen G, Kuang M, Shen N and Chen S. Dysfunctional CD4+, CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis Rheum 2008; 58:801–812.
  23. El-Maraghy N, Ghaly MS, Dessouki O, Nasef SI and Metwally L. CD4+CD25-Foxp3+ T cells as a marker of disease activity and organ damage in systemic lupus erythematosus patients. Arch Med Sci. 2018; 14(5):1033-1040.
  24. Bonelli M, Göschl L, Blüml S, et al., CD4+ CD25-Foxp3+ T cells: A marker for lupus nephritis? Arthritis Res Ther. 2014; 16:104.
  25. Nabil Rafat M., AbdelwahabLotfy, MamdouhAttia, Mahmoud Hadad, Farag Khalil and Marwan Sayed. Study of regulatory T – cells in Systemic Lupus Erythematosus and Rheumatoid Arthritis. Nat Sci 2018; 16(5):38-48.
  26. Lee HY, Hong YK, Yun HJ, Kim YM, Kim JR, Yoo WH. Altered frequency and migration capacity of CD4+CD25+ regulatory T cells in systemic lupus erythematosus. Rheumatology (Oxford) 2008; 47:789–794.
  27. Atfy M, Amr GE, Elnaggar AM, et al. Impact of CD4+CD25high regulatory T-cells and FoxP3 expression in the peripheral blood of patients with systemic lupus erythematosus. The Egyptian Journal of Immunology 2009; 16(1):117-126.
  28. Barâth S, Solt SZ P, E. Kiss, M. Aleksza, M. Zeher and G. Szegedi. The severity of systemic lupus erythematosus negatively correlates with the increasing number of CD4+ CD25highFoxP3+ regulatory T cells during repeated plasmapheresis treatments of patients. Autoimmunity 2007; 40 (7):521 – 528.
  29. Maher SE, Taha HA, Hozayn WG, et al. Study of balance between T-helper 17 /T-regulatory cells in systemic lupus erythematosus and its relation to disease activity. CurrPediatr Res 2019; 23 (2): 49-55.
  30. Santhanam S, Mani M, Tamilselvam TN and Sankaralingam R. ESR, uric acid and its correlation with disease activity in SLE e Is it myth or reality! Indian Rheumatology Association 2015; 0973-3698.
  31. Mirzayan MJ, Schmidt RE and Witte T. Prognostic parameters for flare in systemic lupus erythematosus. Rheumatol (Oxford) 2000; 39:1316-1319.
  32. Chang ER, Abrahamowicz M, Ferland D and Fortin PR. Organ manifestations influence differently the responsiveness of 2 lupus disease activity measures, according to patients or physicians evaluations of recent lupus activity. J Rheumatol 2002; 29:2350-2358.
  33. Ghazali WSW, Daud SMM, Mohammad N and Wong KK. Slicc damage index score in systemic lupus erythematosus patients and its associated factors. Medicine. 2018; 97(42):e12787.
  34. Bruce IN, O'Keeffe AG, Farewell V, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort Annals of the Rheumatic Diseases 2015; 74:1706-1713.

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