Regulatory T-cell levels in systemic lupus erythematosus patients: a meta-analysis

Background The contribution of regulatory T-cells (Tregs) to systemic lupus erythematosus (SLE) pathogenesis remains a matter of debate. The objective of this study was to quantify the association between peripheral blood Tregs and disease status in SLE patients. Method EMBASE and PubMed databases were searched using ‘systemic lupus erythematosus’ and ‘regulatory T-cells’ as relevant key terms. A meta-analysis of studies that examined the proportion of Tregs among peripheral blood mononuclear cells (PBMCs) and CD4+T-cells was performed using Stata software. Subgroup analysis was performed based on ethnic groups and Treg definition markers. Results The Treg/PBMC and Treg/CD4+T-cell ratios were significantly lower in SLE patients than in healthy controls (HCs), whereas patients with active and inactive SLE showed no difference in these indicators. A subgroup analysis indicated that Asian SLE patients had a substantially lower proportion of Tregs/PBMCs than HCs, but this difference was not seen for white and Latin American SLE patients. Patients defined by CD4+CD25+Foxp3+, CD4+CD25+ and CD4+Foxp3+ had a much lower Treg/PBMC ratio compared with HCs. Ethnic groups and choice of Treg definition markers had no influence on the proportion of Tregs/CD4+T-cells. Conclusion The proportion of Tregs among both PBMCs and CD4+T-cells was significantly decreased in SLE patients. Ethnic group and Treg definition markers may influence the proportion of Tregs among PBMCs. Further study of the correlation between SLE disease activity and the proportion of Tregs in peripheral blood is needed to determine the physiological role of this association.

[1]  Xiaofeng Li,et al.  The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis , 2018, Journal of immunology research.

[2]  G. Kirsztajn,et al.  CD4+ T helper cells and regulatory T cells in active lupus nephritis: an imbalance towards a predominant Th1 response? , 2018, Clinical and experimental immunology.

[3]  A. Sahebkar,et al.  Curcumin: A natural modulator of immune cells in systemic lupus erythematosus. , 2017, Autoimmunity reviews.

[4]  L. Metwally,et al.  CD4+CD25-Foxp3+ T cells as a marker of disease activity and organ damage in systemic lupus erythematosus patients , 2016, Archives of medical science : AMS.

[5]  R. González-Amaro,et al.  Patients with Systemic Lupus Erythematosus Show Increased Levels and Defective Function of CD69+ T Regulatory Cells , 2017, Mediators of inflammation.

[6]  J. Todd,et al.  Cells with Treg-specific FOXP3 demethylation but low CD25 are prevalent in autoimmunity , 2017, bioRxiv.

[7]  L. Morel.  Immunometabolism in systemic lupus erythematosus , 2017, Nature Reviews Rheumatology.

[8]  Y. Qiao,et al.  Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency , 2017, Lupus.

[9]  S. Iwata,et al.  B-cell subsets, signaling and their roles in secretion of autoantibodies , 2016, Lupus.

[10]  M. Klinger,et al.  CD4+CD25+CD127− and CD4+CD25+Foxp3+ Regulatory T Cell Subsets in Mediating Autoimmune Reactivity in Systemic Lupus Erythematosus Patients , 2016, Archivum Immunologiae et Therapiae Experimentalis.

[11]  H. Kalim,et al.  Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus , 2016, Clinical Rheumatology.

[12]  Lerisa Govender,et al.  Potential and limitations of regulatory T-cell therapy in solid organ transplantation , 2014, Expert review of clinical immunology.

[13]  L. Riella,et al.  Co-Inhibitory Pathways and Their Importance in Immune Regulation , 2014, Transplantation.

[14]  M. Bauer,et al.  Patients with systemic lupus erythematosus and secondary antiphospholipid syndrome have decreased numbers of circulating CD4⁺CD25⁺Foxp3⁺ Treg and CD3⁻CD19⁺ B cells. , 2014, Revista brasileira de reumatologia.

[15]  P. Boura,et al.  FRI0280 Cd4+cd25highfoxp3+ t regulatory cells as a biomarker of disease activity in systemic lupus erythematosus: a prospective study , 2013, Clinical and experimental rheumatology.

[16]  P. Wiland,et al.  Peripheral blood Th17/Treg imbalance in patients with low-active systemic lupus erythematosus. , 2014, Postepy higieny i medycyny doswiadczalnej.

[17]  D. Hafler,et al.  The plasticity of human Treg and Th17 cells and its role in autoimmunity. , 2013, Seminars in immunology.

[18]  M. Bravo-Zehnder,et al.  Abstracts of the10th International Congress on SLE. April 18-21, 2013. Buenos Aires, Argentina. , 2013, Lupus.

[19]  Dakang Xu,et al.  Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus , 2012, PloS one.

[20]  Weinian Li,et al.  [Expression and significance of Th17 and Treg cells in peripheral blood of patients with systemic lupus erythematosus]. , 2012, Zhonghua yi xue za zhi.

[21]  Jiajia Cui,et al.  Role of Treg Cells and TGF-β1 in Patients with Systemic Lupus Erythematosus: A Possible Relation with Lupus Nephritis , 2012, Immunological investigations.

[22]  J. Alcocer-Varela,et al.  Quantitative and functional profiles of CD4+ lymphocyte subsets in systemic lupus erythematosus patients with lymphopenia , 2011, Clinical and experimental immunology.

[23]  E. Kállas,et al.  Systemic lupus erythematosus exhibits a dynamic and continuum spectrum of effector/regulatory T cells , 2011, Scandinavian journal of rheumatology.

[24]  M. Jaberipour,et al.  Quantification of regulatory T cells in peripheral blood of patients with systemic lupus erythematosus , 2011, Rheumatology International.

[25]  A. Stang.  Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses , 2010, European Journal of Epidemiology.

[26]  Y. Jong,et al.  Altered homeostasis of CD4+ FoxP3+ regulatory T‐cell subpopulations in systemic lupus erythematosus , 2009, Immunology.

[27]  Meenu R Pillai,et al.  The development and function of regulatory T cells , 2009, Cellular and Molecular Life Sciences.

[28]  Xuetao Cao,et al.  CD69+CD4+CD25− T Cells, a New Subset of Regulatory T Cells, Suppress T Cell Proliferation through Membrane-Bound TGF-β11 , 2009, The Journal of Immunology.

[29]  J. Smolen,et al.  Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE). , 2008, International immunology.

[30]  R. Lechler,et al.  Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis , 2008, Clinical and experimental immunology.

[31]  A. Ho,et al.  Reduced CD4+,CD25- T cell sensitivity to the suppressive function of CD4+,CD25high,CD127 -/low regulatory T cells in patients with active systemic lupus erythematosus. , 2008, Arthritis and rheumatism.

[32]  W. Yoo,et al.  Altered frequency and migration capacity of CD4+CD25+ regulatory T cells in systemic lupus erythematosus. , 2008, Rheumatology.

[33]  G. Hamdy,et al.  CD4+CD25+ regulatory T cells (TREG) in systemic lupus erythematosus (SLE) patients: the possible influence of treatment with corticosteroids. , 2008, Clinical immunology.

[34]  J. Alcocer-Varela,et al.  Quantitative and qualitative normal regulatory T cells are not capable of inducing suppression in SLE patients due to T-cell resistance , 2008, Lupus.

[35]  N. Shen,et al.  Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. , 2008, Arthritis and rheumatism.

[36]  S. Zheng,et al.  [Expression of CD4+ CD25+ CD127(low/-) T cells in patients with systemic lupus erythematosus]. , 2008, Zhonghua yi xue za zhi.

[37]  C. Kuo,et al.  The quantitative analysis of peripheral blood FOXP3‐expressing T cells in systemic lupus erythematosus and rheumatoid arthritis patients , 2007, European journal of clinical investigation.

[38]  S. Sipka,et al.  Measurement of natural (CD4+CD25high) and inducible (CD4+IL-10+) regulatory T cells in patients with systemic lupus erythematosus , 2007, Lupus.

[39]  A. Torgashina,et al.  Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus. , 2007, Advances in experimental medicine and biology.

[40]  R. González-Amaro,et al.  Regulatory T cells in patients with systemic lupus erythematosus. , 2006, Journal of autoimmunity.

[41]  C. Gutiérrez,et al.  Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids , 2006, Annals of the rheumatic diseases.

[42]  P. Debré,et al.  Global Natural Regulatory T Cell Depletion in Active Systemic Lupus Erythematosus1 , 2005, The Journal of Immunology.

[43]  E. Bettelli,et al.  Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[44]  A. Fathy,et al.  Diminished CD4+CD25+ T-lymphocytes in peripheral blood of patients with systemic lupus erythematosus. , 2005, The Egyptian journal of immunology.

[45]  L-L Fung,et al.  Decreased CD4+CD25+ T Cells in Peripheral Blood of Patients with Systemic Lupus Erythematosus , 2004, Scandinavian journal of immunology.

[46]  J. Alcocer-Varela,et al.  Quantification of regulatory T cells in patients with systemic lupus erythematosus. , 2003, Journal of autoimmunity.

[47]  J. Goust,et al.  Systemic lupus erythematosus. , 1976, Immunology series.