Mechanisms of Immune Complex–Mediated Neutrophil Recruitment and Tissue Injury

Mayadas, Tanya N.; Tsokos, George C.; Tsuboi, Naotake

doi:10.1161/circulationaha.108.771170

Cited by 177 publications

(149 citation statements)

References 150 publications

(168 reference statements)

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“…Neutrophils are purported to play an active role in the initiation and evolution of coronary arterial plaques (Baetta and Corsini, 2010). Evidently, certain biological characteristics of nascent coronary plaques serve as potent stimuli for neutrophil activation and homing to the evolving lesion (Mayadas et al, 2009). These plaque-infiltrating neutrophils are capable of accelerating the atherosclerotic process, and correspondingly, experimental depletion of neutrophils can decelerate the process (Drechsler et al, 2010;Soehnlein, 2012).…”

Section: Discussionmentioning

confidence: 99%

Relation between neutrophil-to-lymphocyte ratio and severity of coronary artery stenosis

Zhang¹,

Chen²,

Yu³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the relation between the neutrophil-to-lymphocyte ratio (NLR) and the severity of coronary artery stenosis. A total of 219 patients were included in the study, comprising 51 coronary artery atherosclerosis (CAC) patients, 92 stable angina pectoris (SAP) patients, and 76 acute coronary syndrome (ACS) patients. Based on the results of coronary angiography, all patients were divided into two groups according to the Gensini scores: the low-score group (N = 142) and the high-score group (N = 77). The NLR was computed from the ratio of neutrophils and lymphocytes from the complete blood count. The association between the NLR and severity of coronary artery disease was assessed using correlation analysis and logistic regression. The NLR was higher in ACS patients than in SAP and CAC patients (P < 0.05). In addition, the NLR was higher in the high-score group than in the low-score group (P < 0.05). Correlation analysis showed that the NLR was significantly correlated with the Gensini score. After multivariate analysis, high NLRs were independent predictors of high Gensini scores, together with age and high-density lipoprotein. A cutoff NLR of 2.385 predicted high Gensini scores with a sensitivity and specificity of 64 and 63%, respectively. The study suggests that the NLR is an independent Neutrophil-to-lymphocyte ratio and coronary artery stenosis predictor of coronary heart disease that may be useful for predicting the severity of coronary artery stenosis.

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Section: Discussionmentioning

confidence: 99%

Relation between neutrophil-to-lymphocyte ratio and severity of coronary artery stenosis

Zhang¹,

Chen²,

Yu³

et al. 2014

Genet. Mol. Res.

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“…Multiple studies have demonstrated strong and consistent relationships between various inflammatory markers and cardiovascular disease, and the inflammatory process plays a key role in both the initiation and progression of atherosclerosis [20][21][22][23][24] . It has also been demonstrated that the WBC count is an independent predictor of cardiovascular events and all-cause mortality and may be used to identify high-risk individuals without traditional cardiovascular risk factors 14,15,[25][26][27][28] . Regarding stable CAD, parameters of WBCs and their subtypes, including the NLR, have been reported to be associated with the severity of CAD, as determined based on the number of diseased vessel in the early stage.…”

Section: Univariate and Multivariate Analysesmentioning

confidence: 99%

Usefulness of the Neutrophil-to-Lymphocyte Ratio in Predicting the Severity of Coronary Artery Disease: A Gensini Score Assessment

Chen

et al. 2014

JAT

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Aim:The usefulness of the white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR) in predicting the severity of stable coronary artery disease (CAD) has not been sufficiently evaluated, particularly based on strict coronary assessments. The aim of the present study was to investigate the WBC count and NLR in predicting the severity of angiographically proven CAD. Methods: A total of 2,976 CAD patients and 571 non-CAD patients were consecutively enrolled, and the CAD patients were classified into the three groups according to the tertile of the Gensini score (GS, low GS＜18, n = 989; intermediate GS 18-41, n = 995 and high GS＞41, n = 992). The efficacy of the WBC count and NLR in predicting the risk and severity of CAD as well as the correlations between these markers and the GS were analyzed. A receiver operating characteristic (ROC) curve analysis was also performed. Results: The NLR was found to be an independent predictor of both the presence of CAD (OR = 1.18, 95%CI: 1.09-1.27, p = 0.009) and a high GS (OR=1.10, 95%CI: 1.01-1.16, p = 0.032). In addition, there were mild positive correlations between the GS and the NLR, WBC and proportions of neutrophils and monocytes. In the ROC curves analysis, the NLR was found to have the largest area under the curve (AUC = 0.63, 95%CI: 0.59-0.67, p=0.000), with an optimal cut-off value of 2.04 (sensitivity: 62.1%, specificity: 54.8%) for predicting a high GS. Conclusions: The NLR is a valuable independent predictor of the severity of CAD assessed according to the GS. In particular, an NLR of ＞2.04 indicates a higher risk of CAD and greater severity of CAD lesions. Hypertension was diagnosed based on repeated blood pressure measurements of ≥ 140/90 mmHg (at least two times in different environments) or the use of antihypertensive drugs. DM was diagnosed based on a fasting serum glucose level of ≥ 6.99 mmol/L on multiple occasions and/or the use of insulin or oral hypoglycemic agents. Dyslipidemia was diagnosed according to a fasting total cholesterol level of (TC) ≥ 200 mg/dL or triglyceride (TG) level of ≥150 mg/dL. J Atheroscler Laboratory TestsAll baseline laboratory data were acquired from venous blood samples obtained after a 12-hour overnight fast prior to coronary angiography. The levels of WBC, neutrophils, lymphocytes and monocytes were determined using an automated blood cell counter, the Coulter LH780 Hematology Analyzer (Beckman Coulter Ireland Inc. Mervue, Galway, Ireland), and the levels of high-sensitivity C-reactive protein (hs-CRP) were assessed using immunoturbidimetry (Beckmann Assay 360, Bera, California, USA), as previously reported 16,17) . The NLR was calculated as the ratio of neutrophils to lymphocytes, the levels of which were obtained from the same blood samples. The normal range of hs-CRP in our hospital laboratory is 0-3 mg/L. Angiographic ExaminationsSelective coronary angiography was performed in all enrolled subjects using the standard Judkin's technique, and the results were analyzed by at least two interventional physicians w...

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“…B-cell aggregates in disease tissues are characteristic lesions of ongoing immune responses, and these lymphocytes have also been shown to directly exert numerous pathogenic effects (6)(7)(8)(9)(10). Complexes of antigens with the antibodies produced by B cells trigger cytotoxic and proinflammatory cascades (11), and these complexes are present in the circulation (12), bronchoalveolar lavage (13), and lung parenchyma of patients with IPF (5,14). Circulating B-lymphocyte stimulating factor (BLyS), a trophic factor necessary for B-cell survival, maturation, and antibody production, is increased and correlated with the clinical features of patients who have recognized autoantibody-mediated disorders, such as systemic lupus erythematosus and rheumatoid arthritis.…”

mentioning

confidence: 99%

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

Vuga¹,

Tedrow²,

Pandit³

et al. 2014

Am J Respir Crit Care Med

169

115

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Rationale: C-X-C motif chemokine 13 (CXCL13) mediates B-cell trafficking and is increased, proportionately to disease activity, in many antibody-mediated syndromes. Dysregulated B cells have recently been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis.Objectives: To determine if CXCL13 is associated with IPF progression.Methods: CXCL13 was measured in lungs by DNA microarray and immunohistochemistry, and in plasma by ELISA.Measurements and Main Results: CXCL13 mRNA was threefold and eightfold greater in IPF lungs (n = 92) compared with chronic obstructive pulmonary disease (COPD) (n = 191) and normal (n = 108) specimens, respectively (P , 0.0001). IPF lungs also showed increased CXCL13 staining. Plasma CXCL13 concentrations (pg/ml) were greater in 95 patients with IPF (94 6 8) than in 128 subjects with COPD (53 6 9) and 57 normal subjects (35 6 3) (P , 0.0001). Circulating CXCL13 levels were highest in patients with IPF with pulmonary artery hypertension (P = 0.01) or acute exacerbations (P = 0.002). Six-month survival of patients with IPF in the highest quartile of plasma CXCL13 was 65 6 10% versus 93 6 10% in the others (hazard ratio, 5.5; 95% confidence interval, 1.8-16.9; P = 0.0008). CXCL13 increases by more than 50% in IPF serial assays, irrespective of initial values, also presaged respiratory failure (hazard ratio, 7.2; 95% confidence interval, 1.3-40.0; P = 0.008). In contrast, CXCL13 clinical associations in subjects with COPD were limited to modest correlations with FEV 1 (P = 0.05) and progression of radiographic emphysema (P = 0.05).Conclusions: CXCL13 is increased and is a prognostic biomarker in patients with IPF, and more so than in patients with COPD. This contrast indicates CXCL13 overexpressions are intrinsic to IPF, rather than an epiphenomenon of lung injury. The present data implicate CXCL13 and B cells in IPF pathogenesis, and support considerations for trials of specific B-cell-targeted therapies in patients with this intractable disease.

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Mechanisms of Immune Complex–Mediated Neutrophil Recruitment and Tissue Injury

Cited by 177 publications

References 150 publications

Relation between neutrophil-to-lymphocyte ratio and severity of coronary artery stenosis

Relation between neutrophil-to-lymphocyte ratio and severity of coronary artery stenosis

Usefulness of the Neutrophil-to-Lymphocyte Ratio in Predicting the Severity of Coronary Artery Disease: A Gensini Score Assessment

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

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