The immune dysfunction in ankylosing spondylitis patients

Duan, Zhongliang; Gui, Yuyan; Li, Cui; Lin, Jia Wei; Gober, Hans-Jürgen; Qin, Juanxiu; Li, Da‐Jin; Wang, Ling

doi:10.5582/bst.2016.01171

Cited by 25 publications

(23 citation statements)

References 35 publications

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“…Cytokine analysis showed that IL-4 levels in CD4 + T cells were not altered in the AS compared with healthy group. 53 The level of CD8 + T cells, which recognize MHC 1 molecules directly to defend against infections, was also not higher in the AS patients. 54 The results turned out that there was no significant difference in the expression of either CD4 + T cells or CD8 + T cells, while AS patients showed lower percentage of Treg cells.…”

Section: Ank Ylos Ing S P Ondylitismentioning

confidence: 85%

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The role of interleukin‐4 in rheumatic diseases

Chen

et al. 2018

Clin Exp Pharma Physio

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Rheumatism is a group of diseases, most of which are autoimmune diseases, that violate joints, bones, muscles, blood vessels and related soft tissue. As is well known, cytokines play a role in the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritides, and systemic lupus erythematosus. Recently, the role of interleukin-4 (IL-4), which may participate in the mechanism of rheumatism, have been discovered. It is reported that IL-4 takes part in the regulation of T cell activation, differentiation, proliferation, and survival of different T cell types. IL-4 also has an immunomodulatory effect on B cells, mast cells, macrophages, and many cell types. A review of the literature on functions of IL-4 in rheumatic diseases is presented.

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Section: Ank Ylos Ing S P Ondylitismentioning

confidence: 85%

“…The expressions of IL‐4 are also varieties in different research. Cytokine analysis showed that IL‐4 levels in CD4 + T cells were not altered in the AS compared with healthy group . The level of CD8 + T cells, which recognize MHC 1 molecules directly to defend against infections, was also not higher in the AS patients .…”

Section: Ankylosing Spondylitismentioning

confidence: 88%

The role of interleukin‐4 in rheumatic diseases

Chen

et al. 2018

Clin Exp Pharma Physio

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“…Whether and how Tregs participate in the pathogenesis of AS has not been fully elucidated, and data on Tregs in AS patients has been controversial. At present, studies on Tregs in ankylosing spondylitis focus on the number and function of Tregs in patients with ankylosing spondylitis, but the results were not consistent; a reduction [11][12][13], elevation [8,14,15], and no significant change [16,17] in the number of Tregs in AS patients have all been reported. e possible reasons for these discrepant results are mainly due to the ambiguity of Treg surface-specific markers or the degree of disease activity at the time of patient detection.…”

Section: Introductionmentioning

confidence: 87%

Meta-Analysis of Changes in the Number and Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis

Zhou

et al. 2020

BioMed Research International

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Studies on the number and proportion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) patients have been controversial, which has led to a disagreement regarding the role of Tregs in the pathogenesis of AS. To clarify this debate, we conducted a meta-analysis to verify the reported changes in Tregs during AS. We systematically searched the PubMed, Foreign Medical Retrieval System (FMRS), and China National Knowledge Infrastructure (CNKI) web of knowledge databases for eligible articles. A meta-analysis of studies that examined the proportion and number of Tregs among peripheral blood mononuclear cells (PBMCs) and CD4+ T cells was performed using Stata software. Further, subgroup analysis was performed based on Treg definition markers and disease activity to identify potential sources of heterogeneity. Forty-seven studies involving a total of 4373 participants were included in the meta-analysis. The Treg/PBMC and Treg/CD4+ T cell ratios were significantly lower in AS patients than those in healthy controls (HCs). A subgroup analysis indicated that patients defined by CD4+CD25+/high, CD4+CD25+CD127low/−, and CD4+CD25+FOXP3+ had much lower Treg/PBMC and Treg/CD4+ T cell ratios than HCs. Active AS patients also had a substantially lower proportion of Tregs/PBMCs and Treg/CD4+ T cells than HCs. The proportion of Tregs among both PBMCs and CD4+ T cells was significantly decreased in AS patients. Treg definition markers and disease activity may influence the proportion of Tregs measured among the PBMC and CD4+ T cell populations. Further study of the correlation between AS disease activity and the proportion of Tregs in peripheral blood is needed to determine the physiological role of this association. This study implies that loss of Tregs may play a role in the pathogenesis of AS and helps clarify the contradictory Treg results in AS patients. This trial is registered with PROSPERO (CRD42019147064).

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“…6C), terminally differentiated CD8+T cells (CD3+CD8+CD45RA+ CCR7-, Fig. 6.E), and exhausted CD8+T cells (CD3+CD8+CD28-, Fig 6F), at the late stage of differentiation in patients with AS.When analyzing the correlation between C-reactive protein (CRP) levels and lymphocyte frequency, only the frequency of Tc1 cells (CD3+CD8+CXCR3+CCR4-CXCR5-) was found to be negatively correlated with CRP level (r= -0.182, p= 0.041).To understand the correlation between changes in disease status (including CRP, BASDAI, and ASDAS) and changes in lymphocyte frequency after Anbainuo therapy, Spearman's rank correlation analyses showed that the decrease in CRP was positively correlated with the increase in the frequency of Tregs (CD3+CD4+CD25+CD127-) following Anbainuo therapy for 12 weeks (r= 0.489, p=0.018).DiscussionThe inflammatory effects seen throughout AS are associated with abnormal immune function.Previous studies have found changes in the immune cells of patients with AS[6,17,18]. Our study, which included an extensively validated large sample size, showed that active AS causes abnormalities in the proportion of lymphocyte subsets and that help us to indirectly understand the differentiation status, degree of failure, and cell activity of various cell subsets.…”

mentioning

confidence: 58%

“…Studies on acquired immunity to AS have suggested that T-cell-mediated immune regulation may also play an important role [4,5]. CD4+ T and CD8+ T cells and their subsets are known to act on the pathogenesis of AS, although many questions remain about the subject [4,6]. However, there are few detailed reports on the stage of differentiation or subsets of CD4+ T or CD8+ T cells in which AS patients show abnormalities.…”

Section: Tnf-α Inhibitor Therapy Can Improve the Immune Imbalance Of mentioning

confidence: 99%

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

Yang

Wei

et al. 2020

Preprint

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Background: Studies into ankylosing spondylitis (AS) and its relationship with immune function are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune function is unclear.Methods: A total of 40 immune cells were tested with flow cytometry, and the results of 105 HC (healthy control) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed.Results: Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (p<0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (p<0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (p<0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (p<0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (p<0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (p<0.001, 0.0001 and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (p<0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (p<0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of naïve CD4+ T cells had decreased (p<0.05) but Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (p<0.01and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in CRP (C-reactive protein) (r= 0.489, p=0.018). Conclusions: We found that active-stage AS patients have an immunity imbalance involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. TNF-α inhibitor Anbainuo can not only help to inhibit disease activity but can also improve the immune imbalance of CD4+ T cells and negative regulatory cells. But CD8 + T cells have not been rescued.

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The immune dysfunction in ankylosing spondylitis patients

Cited by 25 publications

References 35 publications

The role of interleukin‐4 in rheumatic diseases

The role of interleukin‐4 in rheumatic diseases

Meta-Analysis of Changes in the Number and Proportion of Regulatory T Cells in Patients with Ankylosing Spondylitis

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis

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