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

Background. Accumulating evidence indicates that a deficiency in or dysfunction of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE). As different markers have been used to identify Tregs, recent studies on the proportions of Tregs in SLE patients have...

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Main Authors: Sheng-Xiao Zhang, Xiao-Wen Ma, Yu-Feng Li, Na-Ling Lai, Ze-Hao Huang, Kai Fan, Cai-Hong Wang, Xiao-Feng Li
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/7103219
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author Sheng-Xiao Zhang
Xiao-Wen Ma
Yu-Feng Li
Na-Ling Lai
Ze-Hao Huang
Kai Fan
Cai-Hong Wang
Xiao-Feng Li
author_facet Sheng-Xiao Zhang
Xiao-Wen Ma
Yu-Feng Li
Na-Ling Lai
Ze-Hao Huang
Kai Fan
Cai-Hong Wang
Xiao-Feng Li
author_sort Sheng-Xiao Zhang
collection DOAJ
description Background. Accumulating evidence indicates that a deficiency in or dysfunction of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE). As different markers have been used to identify Tregs, recent studies on the proportions of Tregs in SLE patients have generated controversial results. To clarify the status of Tregs in such patients, we determined the proportions of Tregs present during development of the disease, with special consideration of controversial cellular markers. Methods. We identified studies reporting the proportions of Tregs in SLE patients by searching relevant databases through March 2018. Using the PRISMA guidelines, we performed a random effects meta-analysis of the frequencies of 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. Forty-four studies involving 2779 participants were included in the meta-analysis. No significant difference in the proportions of Tregs was evident between 1772 patients and 1007 controls [−0.191, (−0.552, 0.362), p=0.613, I2=95.7%]. We next conducted subanalyses based on individual definitions of Tregs. When the Treg definition included “FOXP3-positive” cells, the proportions did not differ between SLE patients and controls [−0.042, (−0.548, 0.632), p=0.889, I2=96.6%]; this was the case when Tregs were defined as either “CD25low/−FOXP3+” or “CD25high/+FOXP3+” cells. SLE patients had lower proportions of Tregs that were “single CD25-positive” [−1.428, (−1.982, −0.873), p<0.001, I2=93.4%] and “CD127-negative” [−1.093, (−2.002, −0.183), p=0.018, I2=92.6%] compared to controls. Tregs defined as “CD25bright,” “CD25bright/highCD127low/−,” and “CD25highCD127low/−FOXP3+” did not differ in proportion between SLE patients and controls. Conclusions. The Treg proportions varied by the cellular identification method used. The proportions of Tregs that were accurately identified and functionally validated fell among patients with SLE. Stricter definitions of Tregs are necessary when evaluating the status of such patients.
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spelling doaj-art-049fcc5a2c174075948d90d151b8997d2025-08-20T02:03:06ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/71032197103219The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-AnalysisSheng-Xiao Zhang0Xiao-Wen Ma1Yu-Feng Li2Na-Ling Lai3Ze-Hao Huang4Kai Fan5Cai-Hong Wang6Xiao-Feng Li7Department of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaDepartment of Hematology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaDepartment of Neurology, Shanxi Dayi Hospital Affiliated to Shanxi Medical University, 99 Longcheng Street, Taiyuan, Shanxi 030024, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaBackground. Accumulating evidence indicates that a deficiency in or dysfunction of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE). As different markers have been used to identify Tregs, recent studies on the proportions of Tregs in SLE patients have generated controversial results. To clarify the status of Tregs in such patients, we determined the proportions of Tregs present during development of the disease, with special consideration of controversial cellular markers. Methods. We identified studies reporting the proportions of Tregs in SLE patients by searching relevant databases through March 2018. Using the PRISMA guidelines, we performed a random effects meta-analysis of the frequencies of 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. Forty-four studies involving 2779 participants were included in the meta-analysis. No significant difference in the proportions of Tregs was evident between 1772 patients and 1007 controls [−0.191, (−0.552, 0.362), p=0.613, I2=95.7%]. We next conducted subanalyses based on individual definitions of Tregs. When the Treg definition included “FOXP3-positive” cells, the proportions did not differ between SLE patients and controls [−0.042, (−0.548, 0.632), p=0.889, I2=96.6%]; this was the case when Tregs were defined as either “CD25low/−FOXP3+” or “CD25high/+FOXP3+” cells. SLE patients had lower proportions of Tregs that were “single CD25-positive” [−1.428, (−1.982, −0.873), p<0.001, I2=93.4%] and “CD127-negative” [−1.093, (−2.002, −0.183), p=0.018, I2=92.6%] compared to controls. Tregs defined as “CD25bright,” “CD25bright/highCD127low/−,” and “CD25highCD127low/−FOXP3+” did not differ in proportion between SLE patients and controls. Conclusions. The Treg proportions varied by the cellular identification method used. The proportions of Tregs that were accurately identified and functionally validated fell among patients with SLE. Stricter definitions of Tregs are necessary when evaluating the status of such patients.http://dx.doi.org/10.1155/2018/7103219
spellingShingle Sheng-Xiao Zhang
Xiao-Wen Ma
Yu-Feng Li
Na-Ling Lai
Ze-Hao Huang
Kai Fan
Cai-Hong Wang
Xiao-Feng Li
The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis
Journal of Immunology Research
title The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis
title_full The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis
title_fullStr The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis
title_full_unstemmed The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis
title_short The Proportion of Regulatory T Cells in Patients with Systemic Lupus Erythematosus: A Meta-Analysis
title_sort proportion of regulatory t cells in patients with systemic lupus erythematosus a meta analysis
url http://dx.doi.org/10.1155/2018/7103219
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