Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and Non-Apoptotic Nucleated Cells and Erythrocytes

Hesketh, Emily E.; Dransfield, Ian; Kluth, David; Hughes, Jeremy

doi:10.1371/journal.pone.0131849

Cited by 7 publications

(2 citation statements)

References 71 publications

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“…This further supports the hypothesis that a greater rate of lipid/dead cell accumulation led to enhanced atherosclerosis. IgM antibodies may only be important for efferocytosis in certain contexts, 58 for example, in atherosclerosis where pathways mediating rapid and early apoptotic cell uptake may be defective. Importantly, OSE-specific IgM have been shown to enhance the clearance of apoptotic cells by macrophages in vivo.…”

Section: 44mentioning

confidence: 99%

X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis

Sage

Nus

Chakraborty

et al. 2017

Circulation Research

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Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies, and their importance in both humans and mouse models is still unclear.Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells. Methods and Results:We combined a model of specific antibody deficiency, B cell-specific CD79a-Cre x XBP1 (X-box binding protein-1) floxed mice (XBP1-conditional knockout), with antibody-mediated depletion of CD4+ T cells. Ldlr knockout mice transplanted with XBP1-conditional knockout (or wild-type control littermate) bone marrow were fed western diet for 8 weeks with or without anti-CD4 depletion. All groups had similar levels of serum cholesterol. In Ldlr/ XBP1-conditional knockout mice, serum levels of IgG, IgE, and IgM were significantly attenuated, and local antibody deposition in atherosclerotic plaque was absent. Antibody deficiency significantly accelerated atherosclerosis at both the aortic root and aortic arch. T cell and monocyte responses were not modulated, but necrotic core size was greater, even when adjusting for plaque size, and collagen deposition significantly lower. Anti-CD4 depletion in Ldlr/wild-type mice led to a decrease of serum IgG1 and IgG2c but not IgG3, as well as decreased IgM, associated with increased atherosclerosis and necrotic cores, and a decrease in plaque collagen. The combination of antibody deficiency and anti-CD4 depletion has no additive effects on aortic root atherosclerosis. Conclusions:

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Section: 44mentioning

confidence: 99%

X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis

Sage

Nus

Chakraborty

et al. 2017

Circulation Research

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“…Since natural antibody IgM is suggested to bind to endogenous neoepitopes that are exposed after injury and exacerbates damage [10][11][12][13], whether it is involved in the pathogenesis of LN presented with various types of kidney injury deserves to be investigated. To our knowledge, this is the rst study designed to investigate the clinical relevance of IgM deposition in patients with LN in a large cohort.…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

Wang¹,

JiRong²,

Zhang³

et al. 2021

Preprint

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Background The aim of the study was to investigate the clinical relevance of IgM deposition in patients with LN in a large cohort. Results 217 patients with renal biopsy–proven lupus nephritis were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r=-0.138, P = 0.043; r=-0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributes to glomerular C3 deposition in patients with lupus nephritis (OR = 2.002, 95% CI: 1.295–3.094, P = 0.002). In addition, we also found that patients with IgM 0+-2 + had similar plasma CFH levels, but in patients with IgM3+-4+, plasma CFH levels were significantly lower (300.4 ± 155.8µg/ml vs. 429.9 ± 187.5µg/ml, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1g/d vs. 4.7 ± 3.5g/d, P = 0.037;150.1 ± 121.0µmol/L vs. 105.6 ± 97.1µmol/L, P = 0.005; 0.3 ± 0.2µg/L vs. 0.4 ± 0.2µg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH. Conclusions Our results suggested IgM might bind to injury-associated epitopes and be involved in disease progression and provided a possible relevance of CFH and IgM in the process of alternative pathway (AP) activation.

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Purification of low‐abundance lysozyme in egg white via free‐flow electrophoresis with gel‐filtration chromatography

et al. 2020

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As an effective separation tool, free‐flow electrophoresis has not been used for purification of low‐abundance protein in complex sample matrix. Herein, lysozyme in complex egg white matrix was chosen as the model protein for demonstrating the purification of low‐content peptide via an FFE coupled with gel fitration chromatography (GFC). The crude lysozyme in egg while was first separated via free‐flow zone electrophoresis (FFZE). After that, the fractions with lysozyme activity were condensed via lyophilization. Thereafter, the condensed fractions were further purified via a GFC of Sephadex G50. In all of the experiments, a special poly(acrylamide‐ co‐acrylic acid) (P(AM‐co‐AA)) gel electrophoresis and a mass spectrometry were used for identification of lysozyme. The conditions of FFZE were optimized as follows: 130 μL/min sample flow rate, 4.9 mL/min background buffer of 20 mM pH 5.5 Tris‐Acetic acid, 350 V, and 14 °C as well as 2 mg/mL protein content of crude sample. It was found that the purified lysozyme had the purity of 80% and high activity as compared with its crude sample with only 1.4% content and undetectable activity. The recoveries in the first and second separative steps were 65% and 82%, respectively, and the total recovery was about 53.3%. The reasons of low recovery might be induced by diffusion of lysozyme out off P(AM‐co‐AA) gel and co‐removing of high‐abundance egg ovalbumin. All these results indicated FFE could be used as alternative tool for purification of target solute with low abundance.

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Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and Non-Apoptotic Nucleated Cells and Erythrocytes

Cited by 7 publications

References 71 publications

X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis

X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

Purification of low‐abundance lysozyme in egg white via free‐flow electrophoresis with gel‐filtration chromatography

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