The CD27–CD70 pathway and pathogenesis of autoimmune disease

Han, Bobby Kwanghoon; Olsen, Nancy J.; Bottaro, Andrea

doi:10.1016/j.semarthrit.2015.08.001

Cited by 66 publications

(59 citation statements)

References 77 publications

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“…CD70 on activated antigen-presenting cells, including B cells, interacts with CD27 and provides costimulatory signals in addition to T cell receptor. The CD27-CD70 interaction is primarily regulated by expression of CD70, which is induced by Toll-like receptors (TLR), CD40, and/or antigen receptor signaling [9, 10]. …”

Section: Discussionmentioning

confidence: 99%

“…However, other studies found that CD27-CD70 signal-blocking prevented EAE in SJL/J mice [22] and the overexpression of CD70 in B cells enhanced EAE in 2D2 mice [23]. Although the role of CD27-CD70 in Th17 regulation is inconsistent, maybe due to the pleiotropic and complex effects of CD70-CD27 interaction on T cell and B cell activation [9, 10], CD27-CD70 is sure to be one of the components of the Th17 pathway. Interestingly, Th17 proportion and IL-17A level were elevated in patients with NMOSD in our previous study [4].…”

Section: Discussionmentioning

confidence: 99%

“…CD27-CD70 signaling facilitates the proliferation and survival of activated T cells and B cells [9, 10]. CD27 is expressed in about 80% of peripheral blood T lymphocytes as a transmembrane homodimer with subunits of 50–55 kDa [11, 12].…”

Section: Introductionmentioning

confidence: 99%

“…It is not expressed by naïve B cells but is upregulated in activated and antigen-experienced B cells. A soluble form of CD27 (sCD27; 30–32 kDa) can be cleaved from the membrane-bound form on activated T cells through the action of matrix metalloproteinase [9, 10]. CD27 ligation is characterized by CD70 which is expressed on activated antigen-presenting cells including B cells [9, 10].…”

Section: Introductionmentioning

confidence: 99%

“…A soluble form of CD27 (sCD27; 30–32 kDa) can be cleaved from the membrane-bound form on activated T cells through the action of matrix metalloproteinase [9, 10]. CD27 ligation is characterized by CD70 which is expressed on activated antigen-presenting cells including B cells [9, 10]. Consequently, CD27 is an attractive candidate for contributing to a variety of autoimmune processes in which T cell-B cell collaboration plays a role in pathogenesis, e.g., MS and NMOSD.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Liu¹,

Zhong²,

Liu³

et al. 2018

Neuroimmunomodulation

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Object: CD27 belongs to the tumor necrosis factor receptor family and is constitutively expressed on T cells. The concentration of cerebrospinal fluid (CSF) soluble (s)CD27 is elevated in patients with multiple sclerosis (MS). However, whether the level of CSF sCD27 is elevated in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. The aim of this study was to measure the CSF concentration of sCD27 and to determine its relationship with NMOSD disease activity. Methods: CSF CXCL13 was measured by ELISA in neuromyelitis optica (NMO) (n = 31) and MS (n = 23) patients and in controls (CTLs) (n = 22). Results: The concentration of sCD27 was higher in the NMO group than in the MS (p = 0.082) and CTL (p = 0.002) groups, and there was a positive correlation with CSF IL-6 (p = 0.000) and a negative correlation with IL-10 (p = 0.073). In the NMO group, patients with higher sCD27 concentrations exhibited worse disease disability in their CSF (p = 0.006). Moreover, the sCD27 concentrations had a significantly positive correlation with the level of CSF total protein (p = 0.030). Furthermore, the patients positive for AQP4-IgG (n = 26) seemed to have higher levels of sCD27 in their CSF (p = 0.069) than those negative for AQP4-IgG (n = 5). Conclusions: We revealed that the level of CSF sCD27 was elevated in NMOSD and correlated with NMOSD disease activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Liu¹,

Zhong²,

Liu³

et al. 2018

Neuroimmunomodulation

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Soluble CD27 Levels in Cerebrospinal Fluid as a Prognostic Biomarker in Clinically Isolated Syndrome

et al. 2017

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IMPORTANCE There is a growing number of therapies that could be administered after the first symptom of central nervous system demyelination. These drugs can delay multiple sclerosis (MS) diagnosis and slow down future disability. However, treatment of patients with benign course may not be needed; therefore, there is a need for biomarkers to predict long-term prognosis in patients with clinically isolated syndrome (CIS).OBJECTIVE To investigate whether the T-cell activation marker soluble CD27 (sCD27) measured in cerebrospinal fluid of patients at time of a first attack is associated with a subsequent diagnosis of MS and a higher relapse rate. DESIGN, SETTING, AND PARTICIPANTSThis prospective study included 77 patients with CIS between March 2002 and May 2015 in a tertiary referral center for multiple sclerosis, in collaboration with several regional hospitals. Patients with CIS underwent a lumbar puncture and magnetic resonance imaging scan within 6 months after first onset of symptoms.MAIN OUTCOMES AND MEASURES Soluble CD27 levels were determined in cerebrospinal fluid using a commercially available enzyme-linked immunosorbent assay. Cox regression analyses was used to calculate univariate and multivariate hazard ratios for MS diagnosis. Association between sCD27 levels and relapse rate was assessed using a negative binomial regression model. RESULTS Among 77 patients with CIS, 50 were female (79.5%), and mean (SD) age was 32.7 (7.4) years. Mean (SD) age in the control individuals was 33.4 (9.5) years, and 20 were female (66.7%).Patients with CIS had higher cerebrospinal fluid sCD27 levels than control individuals (geometric mean, 31.3 U/mL; 95% CI, 24.0-40.9 vs mean, 4.67 U/mL; 95% CI, 2.9-7.5; P < .001). During a mean (SD) follow-up of 54.8 (35.1) months, 39 of 77 patients (50.6%) were diagnosed as having MS. In a model adjusted for magnetic resonance imaging and cerebrospinal fluid measurements, sCD27 levels were associated with a diagnosis of MS (hazard ratio, 2.4 per 100 U/mL increase in sCD27 levels; 95% CI, 1.27-4.53; P = .007). Additionally, patients with MS with high sCD27 levels (median, >31.4 U/mL) at the time of CIS had a 5.5 times higher annualized relapse rate than patients with low sCD27 levels (annualized relapse rate, 0.06 vs 0.33; P = .02).CONCLUSIONS AND RELEVANCE Soluble CD27 in cerebrospinal fluid of patients with CIS was associated with MS diagnosis and a high relapse rate. Therefore, sCD27 is an activation molecule directly related to the immunopathology of the disease and is a potential clinical marker to help in treatment decisions after a first attack of suspected MS.

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Identification and Characterization of CD8⁺CD27⁺CXCR3⁻ T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus

Zhang,

Du,

Jin

et al. 2023

Advanced Science

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Systemic Lupus Erythematosus (SLE) etiopathogenesis highlights the contributions of overproduction of CD4+ T cells and loss of immune tolerance. However, the involvement of CD8+ T cells in SLE pathology and disease progression remains unclear. Here, the comprehensive immune cell dysregulation in total 263 clinical peripheral blood samples composed of active SLE (aSLE), remission SLE (rSLE) and healthy controls (HCs) is investigated via mass cytometry, flow cytometry and single‐cell RNA sequencing. This is observed that CD8+CD27+CXCR3− T cells are increased in rSLE compare to aSLE. Meanwhile, the effector function of CD8+CD27+CXCR3− T cells are overactive in aSLE compare to HCs and rSLE, and are positively associated with clinical SLE activity. In addition, the response of peripheral blood mononuclear cells (PBMCs) is monitored to interleukin‐2 stimulation in aSLE and rSLE to construct dynamic network biomarker (DNB) model. It is demonstrated that DNB score‐related parameters can faithfully predict the remission of aSLE and the flares of rSLE. The abundance and functional dysregulation of CD8+CD27+CXCR3− T cells can be potential biomarkers for SLE prognosis and concomitant diagnosis. The DNB score with accurate prediction to SLE disease progression can provide clinical treatment suggestions especially for drug dosage determination.

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The CD27–CD70 pathway and pathogenesis of autoimmune disease

Cited by 66 publications

References 77 publications

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Soluble CD27 Levels in Cerebrospinal Fluid as a Prognostic Biomarker in Clinically Isolated Syndrome

Identification and Characterization of CD8⁺CD27⁺CXCR3⁻ T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus

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The CD27–CD70 pathway and pathogenesis of autoimmune disease

Cited by 66 publications

References 77 publications

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder

Soluble CD27 Levels in Cerebrospinal Fluid as a Prognostic Biomarker in Clinically Isolated Syndrome

Identification and Characterization of CD8+CD27+CXCR3− T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus

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Identification and Characterization of CD8⁺CD27⁺CXCR3⁻ T Cell Dysregulation and Progression‐Associated Biomarkers in Systemic Lupus Erythematosus