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

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 cl...

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Main Authors: Na-Lin Lai, Sheng-Xiao Zhang, Jia Wang, Jia-Qian Zhang, Cai-Hong Wang, Chong Gao, Xiao-Feng Li
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/1058738
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author Na-Lin Lai
Sheng-Xiao Zhang
Jia Wang
Jia-Qian Zhang
Cai-Hong Wang
Chong Gao
Xiao-Feng Li
author_facet Na-Lin Lai
Sheng-Xiao Zhang
Jia Wang
Jia-Qian Zhang
Cai-Hong Wang
Chong Gao
Xiao-Feng Li
author_sort Na-Lin Lai
collection DOAJ
description 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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spelling doaj-art-dccf662de2a24a8381465f5f7a949cc32025-08-20T03:23:56ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/10587381058738The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-AnalysisNa-Lin Lai0Sheng-Xiao Zhang1Jia Wang2Jia-Qian Zhang3Cai-Hong Wang4Chong Gao5Xiao-Feng Li6Department 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, ChinaDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USADepartment of Rheumatology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi 030001, ChinaObjective. 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.http://dx.doi.org/10.1155/2019/1058738
spellingShingle Na-Lin Lai
Sheng-Xiao Zhang
Jia Wang
Jia-Qian Zhang
Cai-Hong Wang
Chong Gao
Xiao-Feng Li
The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis
Journal of Immunology Research
title The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis
title_full The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis
title_fullStr The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis
title_full_unstemmed The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis
title_short The Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis: A Meta-Analysis
title_sort proportion of regulatory t cells in patients with ankylosing spondylitis a meta analysis
url http://dx.doi.org/10.1155/2019/1058738
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