Lower expression levels of the programmed death 1 receptor on CD4+CD25+ T cells and correlation with the PD‐1.3A genotype in patients with systemic lupus erythematosus

Kristjánsdóttir, Helga; Steinsson, Kristján; Gunnarsson, Iva; Gröndal, Gerður; Erlendsson, Kristján; Alarcón‐Riquelme, Marta E.

doi:10.1002/art.27417

Cited by 61 publications

(55 citation statements)

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“…Importantly, the same genotype that was correlated with increased risk to develop the disease also correlated with reduced expression of the PD-1 receptor [23,25]. Despite the lack of data regarding the genetic polymorphism of PD-1 in the current study, the inverse correlation between PD-1 expression and disease activity implies a similar pathogenic role for PD-1.…”

Section: Discussioncontrasting

confidence: 51%

“…PD-1 polymorphism has been linked to several autoimmune diseases, including systemic lupus erythematosus, ankylosing spondylitis, and multiple sclerosis [22][23][24], indirectly implying a role of PD-1 in the pathogenesis of these diseases. Importantly, the same genotype that was correlated with increased risk to develop the disease also correlated with reduced expression of the PD-1 receptor [23,25].…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis

et al. 2015

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Programmed death-1 (PD-1) is an inhibitory co-receptor that is highly expressed in T lymphocytes that has been shown to downregulate inflammatory responses in several inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis. Yet, the role of PD-1 in psoriatic arthritis (PsA) has not been studied. In order to fill this gap, we measured the expression levels of PD-1 in peripheral T cells from patients with active disease. Twenty patients and fifteen age-matched healthy control subjects were recruited. The percentage of CD3(+)PD-1(+) T cells was measured by flow cytometry. Despite normal concentration of peripheral T cells, the expression levels of PD-1 were significantly higher in patients compared to healthy controls. Interestingly, among the patients, the expression levels inversely correlated with disease activity measured by disease activity scores (DAS28). PD-1 expression levels strongly correlated with the number of tender and swollen joints, but not with C-reactive protein (CRP) levels or psoriasis area and severity index (PASI). Functionally, in vitro ligation of PD-1 receptor in PsA T cells inhibited interleukin-2 (IL-2) secretion, Akt phosphorylation, and Rap1 activation. These findings suggest that PD-1 might serve as a biomarker for disease activity in PsA and highlight the need for additional studies in order to establish the role of PD-1 in PsA pathogenesis.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis

et al. 2015

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“…Abrogation of PD-1 signaling enhanced TFH cells numbers and initial immunoglobulin responses, especially early in the GCs response (27). Recent studies had elucidated that the expression of PD-1 in patients with active SLE and RA was significantly lower than the healthy population (28,29). However, our study demonstrated that there was a higher expression of PD-1 in MG patients with thymoma compared with NMG and CTL group.…”

Section: Discussionmentioning

confidence: 44%

Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

et al. 2016

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Results: Higher percentage of thymic TFH cells was found in MG patients with thymoma compared with both thymoma patients without MG and control group. The expression levels of the four markers in thymoma of MG patients were significantly higher than thymoma patients without MG and control group.No significant difference was found in the levels of programmed cell death 1 (PD-1) and Bcl-6 between thymoma patients without MG and the control, while the levels of CXCR5 and ICOS in thymoma patients without MG were higher than control group. Conclusions: These results suggested thymic TFH cells might involve in the pathogenesis of MG with thymoma. However, it needs further study to test if the inhibition of the function of TFH cells could effectively alleviate the severity of MG. 11,12). These cells are characterized by increased expression of numerous molecules including inducible co-stimulator (ICOS), program death 1 (PD-1) and CD40-ligand, the transcription factor B cell lymphoma 6 (Bcl-6) and regulatory cytokines which can promote the development of TFH cells and the interaction of T and B cells (13). Increased numbers of circulating TFH cells and aberrant activation of TFH cells are associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and IgA nephropathy (14-17). Keywords: Myasthenia gravis (MG); thymoma; T follicular helper cells (TFH cells)The numbers of TFH cells in peripheral blood of MG patients are significantly higher than that of healthy control, and the frequency of TFH cells are positively correlated with levels of serum AchR-Ab (18). However, the thymic TFH cells in thymoma patients with MG remain controversial (19,20). In this study, we investigated the percentage of thymic TFH cells around the thymoma region and their activity in thymoma patients with MG. Materials and methods SamplesA total of 50 patients were enrolled who underwent thymectomy at the Department of Thoracic Surgery, Huashan Hospital of FDU between 2013 and 2014. Thirty thymoma patients with MG were recruited as MG group (MG) while another twenty thymoma patients without MG were recruited as non-MG group (NMG). We collected ten control thymic biopsies from cardiac surgery cases of the Department of Cardiovascular Surgery, Huashan Double-labeled immunofluorescence (IF)Endogenous peroxide activity quench were performed with protocols similar to IHC staining. Tissues were incubated with rabbit anti-human CD4 antibody (EPR6855, Abcam) at 37 ℃ for 4 h. Tissues were incubated with mouse antihuman CXC chemokine receptor 5 (CXCR5) monoclonal antibody (Clone51505, Abcam) at 37 ℃ for 24 h. Sections were incubated with Goat anti-Rabbit IgG-heavy and light chain cross-adsorbed antibody dylight ® 488-conjugated affinipure (A90-516D2, Bethyl, USA) at 37 ℃ for 2 h. Sections were incubated with goat anti-mouse IgGheavy and light chain cross-adsorbed antibody dylight ® 594-conjugated affinipure (A120-201D4; Bethyl, USA) at 37 ℃ for 2 h. Finally, the sections were mounted and cov...

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“…Polymorphisms in the CTLA-4 gene have been linked to several autoimmune diseases as rheumatoid arthritis (Rodriguez et al, 2002), type I diabetes (Kavvoura and Ioannidis, 2005) and granulomatosis with polyangiitis (Wegener's) (Giscombe et al, 2002;Huang et al, 2000a;Slot et al, 2008;Zhou et al, 2004). In addition several reports show a relationship between these polymorphisms and a reduction in the expression or in the inhibitory function of CTLA-4 (Huang et al, 2000b;Kouki et al, 2000;Kristjansdottir et al, 2010;Ligers et al, 2001).…”

Section: Introductionmentioning

confidence: 94%