The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis

Zhang, Sheng‐Xiao; Ma, Xiaowen; Li, Yufeng; Lai, Na-Ling; Huang, Zehao; Fan, Kai; Wang, Caihong; Li, Xiaofeng

doi:10.1155/2018/7103219

Cited by 26 publications

(23 citation statements)

References 69 publications

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“…However, studies about CS and DMARDs on peripheral blood Tregs in AS patients are still lacking. In addition to drugs, disease activity also affects the proportion of peripheral blood Tregs [81, 82]. But our subgroup analysis found no difference in the proportion of Tregs in patients with active compared with stable AS.…”

Section: Discussionmentioning

confidence: 92%

The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis

Lai

Zhang

Jia

et al. 2019

Journal of Immunology Research

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Objective Accumulating evidence indicates that regulatory T cells (Tregs) may be involved in the pathogenesis of ankylosing spondylitis (AS). As different markers have been used to identify Tregs, some studies on the proportions of Tregs in AS patients have generated considerable controversy. To clarify the status of Tregs in such patients, we determine the proportion changes of peripheral Tregs during development of the disease, with different cellular markers. Methods We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in AS patients. Using the PRISMA guidelines, we performed a random-effects meta-analysis of the frequencies of peripheral Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests. Results A total 29 studies involving 1732 participants were included in the meta-analysis. Their conclusions of using the diversity of Tregs surface markers were inconsistent with each other. No significant difference in the proportions of Tregs was evident regardless of the definitions used [−0.709, (−1.455, 0.037, p = 0.063), I2 = 97.3%]. Six studies used “single CD25-positive” cells as Tregs, which revealed a significant increase in AS patients compared with healthy blood donors [0.736, (0.138, 1.334), p = 0.016, I2 = 80.7%]. Notably, the proportions of “CD4+CD25+FOXP3+,” “CD4+CD25highCD127low/−,” or “CD4+CD25+CD127low” T cells were lower in AS patients [−2.856, (−4.645, −1.066), p = 0.002; −1.812, (−2.648, −0.977), p < 0.001; −1.12, (−1.605, −0.635), p < 0.001]. Tregs defined as “CD25high,” “CD25bright,” “CD25bright/highCD127low/−,” “CD4+FOXP3+,” “CD4+CD25highFOXP3+,” and “CD4+CD25+CD127−” did not differ in proportion between AS patients and healthy blood donors. Conclusions The levels of Tregs varied based on the cellular identification markers used. The proportions of CD4+CD25+FOXP3+Tregs, CD4+CD25highCD127low/−, or CD4+CD25+CD127low in blood of AS patients were significantly decreased as compared with those in healthy blood donors, and our findings lend support to the idea that the Treg status of AS patients is important. And we recommend the above as the best definition of Tregs when evaluating the status of such patients.

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Section: Discussionmentioning

confidence: 92%

The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis

Lai

Zhang

Jia

et al. 2019

Journal of Immunology Research

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“…[23][24][25] A recent meta-analysis found that the proportion of Tregs in patients with active SLE was lower than that in patients in remission, suggesting that SLE activity is related to a decrease in Treg numbers. 26 Similarly, Miao et al 9 showed that a decrease in the absolute number of circulating CD4 + Tregs, rather than an increase in either the absolute number or proportion of Th17 cells, crucially affected the immune disorders of pSS patients; pSS is also a chronic, autoantigenmediated inflammatory disease. Tregs inhibit the proinflammatory activity of macrophages, which are the principal immune effector cells in patients with TNFmediated psoriasis.…”

Section: Discussionmentioning

confidence: 99%

The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2

Jia

Zhang

Hao

et al. 2020

Therapeutic Advances in Chronic Disease

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Background: Although regulatory T cells (Tregs) play crucial roles in the maintenance of immune hemostasis, the numbers of peripheral Tregs in patients with psoriatic arthritis (PsA) remain unclear. We measured these numbers and the efficacy and safety of low-dose interleukin-2 (IL-2) therapy. Methods: We recruited 95 PsA patients, of whom 22 received subcutaneous low-dose IL-2 [0.5 million international units (MIU) per day for 5 days] combined with conventional therapies. The absolute numbers of cells in peripheral CD4+ T cell subsets were measured via modified flow cytometry. Clinical and laboratory indicators were compared before and after treatment. Results: PsA patients had lower peripheral Treg numbers than healthy controls ( p < 0.01), correlating significantly and negatively with the levels of disease indicators ( p < 0.05). Although low-dose IL-2 significantly increased the Th17 and Treg numbers in PsA patients compared with the baseline values, the Treg numbers rose much more rapidly than those of Th17 cells, re-balancing the Th17 and Treg proportions. Low-dose IL-2 combination therapy rapidly reduced PsA disease activities as indicated by the DAS28 instrument, thus the number of tender joints, visual analog scale pain, physician global assessment, the dermatology life quality index score, and the health assessment questionnaire score (all p < 0.05). Conclusion: PsA patients exhibited low Treg numbers. Low-dose IL-2 combination treatment increased these numbers and relieved disease activity without any apparent side effects. Additional studies are required to explore the long-term immunoregulatory utility of IL-2 treatment.

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“…Recently, Zhang et al (51) performed a systemic review on a similar topic, but mainly focused on establishing the alteration of Treg frequency in SLE. However, in our meta-analysis the changes in the frequency and absolute number of Tregs were calculated along with a systemic analysis of the effects of treatment, disease severity, and organ involvement on Tregs.…”

Section: Discussionmentioning

confidence: 99%

The Regulatory T Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-Analysis

Deng

Yang

et al. 2019

Front. Immunol.

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Background: Regulatory T cells (Tregs) researches in systemic lupus erythematosus (SLE) have floundered over the years, reports on the numbers and function of Tregs in SLE present quite contradictory results. We therefore conducted a meta-analysis to verify the changes of Tregs in active SLE. Methods: We systematically searched PubMed, Embase, and ISI web of knowledge databases for eligible articles. In total, 628 active SLE patients and 601 controls from 18 studies were included. Due to a high degree of heterogeneity, a random effects model was used to assess the mean differences in Treg percentages, absolute numbers, and suppression capacities of Tregs between active SLE and controls. Further, subgroup analysis was performed to identify potential sources of heterogeneity. Results: The pooled percentages of Tregs in active SLE patients were found to be lower than those in controls (−0.864 ± 0.308, p = 0.005), with great heterogeneity ( I 2 = 95.01). The discrepancy of published results might result from the following differences among studies: gating strategies for Tregs, diagnostic criteria for SLE, and thresholds of SLEDAI chosen to differentiate between active and inactive SLE. In active SLE, Tregs gated based on CD25 alone showed lower pooled frequency than those gated by Foxp3 + or CD127 low/∅ . The percentages of Tregs in active SLE was significantly lower than that in controls when the enrolled SLE patients were diagnosed according to the 1997 modified criteria, whereas they were comparable to controls when diagnosed by the 1982 criteria; the higher threshold of SLEDAI score used to define active SLE tended to achieve a lower percentage of Tregs. The pooled absolute numbers of Tregs in active SLE were significantly decreased compared to those in controls (−1.328 ± 0.374, p < 0.001), but seemed to be unaffected by gating strategies. Suppression capacities of Tregs from active SLE patients showed no abnormalities based on the limited pooled data. Longitudinal monitoring of active SLE showed a significant decrease in Treg percentage at remission. Conclusions: This study implies that loss of Tregs may play a role in the pathogenesis of active SLE and help clarify contradictory Treg results in SLE.

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The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis

Cited by 26 publications

References 69 publications

The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis

The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis

The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2

The Regulatory T Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-Analysis

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