Association between CD40 polymorphisms and systemic lupus erythematosus and correlation between soluble CD40 and CD40 ligand levels in the disease: a meta-analysis

Bae, Sang Cheol; Lee, Young Ho

doi:10.1177/0961203319878822

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…Much less is known about the possible role of sCD40 as a marker for CVD. Though sCD40 appears to be actively produced under physiological conditions (as suggested by comparatively large amounts of sCD40 found in urine of healthy individuals), 28 elevated plasma levels of sCD40 has nonetheless been described in pathologies such as systemic lupus erythematosus, 29 slow coronary flow phenomenon 30 and early Alzheimer's disease. 31 In the SUMMIT cohort, we found higher plasma sCD40 levels in individuals that had suffered a prior ischemic stroke or MI or were hypertensive.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype

et al. 2021

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Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability.Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling.Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

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Section: Discussionmentioning

confidence: 99%

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype

et al. 2021

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“…Soluble CD40 was found to be the strongest predictor of atherosclerotic plaque burden in the carotid artery bifurcation, among several other markers tested [30]. A role for sCD40 as a biomarker was also suggested in several other inflammatory diseases such as, e.g., ulcerative colitis [31], systemic sclerosis [32], and lupus erythematosus [33].…”

Section: Discussionmentioning

confidence: 88%

Ectodomain Shedding by ADAM17 Increases the Release of Soluble CD40 from Human Endothelial Cells under Pro-Inflammatory Conditions

Klersy,

Meyer,

Leuschner

et al. 2023

Cells

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Background: Homozygosity for the C allele of the −1T>C single nucleotide polymorphism (SNP) of the CD40 gene (rs1883832) is associated with susceptibility to coronary heart disease (CHD), enhanced CD40 expression, and shedding. The disintegrin metalloprotease ADAM17 can cleave various cell surface proteins. This study investigates an association between ADAM17-mediated CD40 shedding and inflammation in CC genotype human endothelial cells. Methods: Human umbilical vein endothelial cells (HUVEC) carrying the CC genotype were stimulated with soluble CD40 ligand (sCD40L) or tumor necrosis factor-α (TNFα). Messenger RNA and protein expression were determined with standard methods. Levels of high sensitive c-reactive protein (hs-CRP), interleukin-6 (IL-6), and sCD40 in plasma samples from patients with CHD were assessed using ELISA. Results: ADAM17 surface abundance was elevated following stimulation with CD40L and TNFα just as its regulator iRhom2. Inhibition of ADAM17 prevented TNFα-induced sCD40 and soluble vascular cell adhesion molecule-1 release into the conditioned medium and reinforced CD40 surface abundance. Secondary to inhibition of ADAM17, stimulation with CD40L or TNFα upregulated monocyte chemoattractant protein-1 mRNA and protein. Levels of sCD40 and the inflammatory biomarkers hs-CRP and IL-6 were positively correlated in the plasma of patients with CHD. Conclusions: We provide a mechanism by which membrane-bound CD40 is shed from the endothelial cell surface by ADAM17, boosting sCD40 formation and limiting downstream CD40 signaling. Soluble CD40 may represent a robust biomarker for CHD, especially in conjunction with homozygosity for the C allele of the −1T>C SNP of the CD40 gene.

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“…It is important to mention that the majority of the previously published studies concerning CD40 in SLE assessed its soluble form or encoding gene polymorphisms, and reported possible associations with SLE susceptibility without data about the role of peripheral CD40 + B cells. 9 However, Tokunaga et al. in his pilot study administrated rituximab in five patients with refractory SLE and reported a statistically significant decrease in peripheral CD40 + B cells from 94.6% to 55.5% after remission, with a dramatic improvement in SLEDAI.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 A recent meta-analysis proved the association between CD40 polymorphisms and SLE, and confirmed the important role of CD40 in SLE pathogenesis. 9 CD40 and CD40L interaction is essential to stimulate immunoglobulin class switching, as well as T cell–dependent B-cell response. 10 Following the interaction with CD40L, high expression of CD40 on antigen-presenting cells could enhance signalling in patients with autoimmune diseases such as SLE.…”

Section: Introductionmentioning

confidence: 99%

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CD40 and CD72 expression and prognostic values among children with systemic lupus erythematosus: a case–control study

Asmiyou

Bakr

Shahin

et al. 2020

Lupus

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Systemic lupus erythematosus (SLE) is a chronic disease with proven interactions between immune system components, including both humoral- and cell-mediated immunity, as well as co-stimulatory and inhibitory molecules such as CD40 and CD72. Here, we investigated CD40 and CD72 expression on B cells of SLE children and assessed their prognostic values. We conducted a preliminary case–control study in Mansoura University Children's Hospital, Egypt from September 2018 to January 2020 including 27 SLE children and 27 healthy controls. We assessed cases during initial flare and after remission. Flow cytometry analysis was carried out for all participants for CD40 and CD72 expression of B cells. During flare, SLE cases had statistically significant higher CD40 and lower CD72 expression in comparison with controls ( p < 0.001). After remission, the number of CD40+ B cells significantly decreased ( p < 0.001), while the number of CD72+ B cells significantly increased ( p < 0.001) in comparison with flare. We reported non-significant positive correlations between CD40 expression and SLE Disease Activity Index (SLEDAI; p = 0.347 during flare and p = 0.653 after remission) and negative correlations between CD72 expression and SLEDAI ( p = 0.34 during flare and p = 0.044 after remission). No significant differences were detected between renal histopathology classes with regard to CDs expression on B cells ( p = 0.45 for CD40 and p = 0.63 for CD72). In conclusion, CD40+ B cells and CD72+ B cells could be considered as markers of paediatric SLE flare and remission, respectively.

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Association between CD40 polymorphisms and systemic lupus erythematosus and correlation between soluble CD40 and CD40 ligand levels in the disease: a meta-analysis

Cited by 7 publications

References 36 publications

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype

Ectodomain Shedding by ADAM17 Increases the Release of Soluble CD40 from Human Endothelial Cells under Pro-Inflammatory Conditions

CD40 and CD72 expression and prognostic values among children with systemic lupus erythematosus: a case–control study

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