Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Xu, Ruonan; Lin, Fang‐Yue; Bao, Chunmei; Huang, Huihuang; Ji, Chengcheng; Wang, Siyu; Jin, Lei; Sun, Lijian; Li, Ké; Zhang, Zheng; Wang, Fusheng

doi:10.1038/cmi.2014.136

Cited by 35 publications

(32 citation statements)

References 22 publications

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“…It was revealed that septic patients had low expression levels of C5aR and C5L2 on neutrophils compared to healthy and SIRS cases, and this expression pattern was correlated with disease severity. [29]…”

Section: Neutrophil Dysfunction In Sepsismentioning

confidence: 99%

Neutrophil Dysfunction in Sepsis

Zhang

Liu

Gao

et al. 2016

Chinese Medical Journal

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Objective:Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis.Data Sources:Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of “neutrophil function”, “neutrophil dysfunction”, and “sepsis”.Study Selection:Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis.Results:We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis.Conclusions:Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed.

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Section: Neutrophil Dysfunction In Sepsismentioning

confidence: 99%

Neutrophil Dysfunction in Sepsis

Zhang

Liu

Gao

et al. 2016

Chinese Medical Journal

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“…In clinical practice, it is di cult to distinguish among the C3 species related to the outcome because circulating C3 exists in different sizes [25]. It is also di cult to detect C5a due to its low plasma concentration [13]. CFH is one of the most abundant complement components in human blood [7]; therefore, CFH may represent a potential candidate biomarker for excessive complement activation.…”

Section: Discussionmentioning

confidence: 99%

“…The rapid activation of the complement system plays an important role in defending against pathogens; however, the excessive complement activation in sepsis has been reported that to produce the detrimental effects; including neutrophil dysfunction [12,13], coagulopathy [14], and organ failure, leading to a poor outcome [15]. However, it is unclear whether CFH is associated with severity, mortality and organ dysfunction in patients with sepsis.…”

Section: Introductionmentioning

confidence: 99%

Association between plasma complement factor H concentration and clinical outcomes in patients with sepsis

Shimizu

Fujino

Sawai

et al. 2020

Preprint

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Background The complement system is important for defending against pathogens; however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway.This study aimed to investigate the association between plasma CFH levels on admission to the ICU and 90-day mortality and organ dysfunction, in patients with sepsis. Methods This is a single-center prospective observational study conducted from July 2016 to March 2019. Logistic regression analysis and correlation analysis were performed to assess the relationship between the plasma CFH on admission to the ICU and 90-day mortality, and organ dysfunction. Results This analysis included 62 patients. The plasma CFH levels were significantly lower in 90 day non survivors than those in survivors (70.0 μg/ml [interquartile range (IQR) 51.2 - 97.6] vs 104.8 μg/ml [IQR 66.8 - 124.2] , P=0.006) . The plasma CFH levels were associated with 90 day mortality (OR 0.977 95% CI 0.957 – 0.994, p = 0.01). Correlation analysis showed that the plasma CFH levels were negatively correlated with the Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score 2 (SAPS 2) (r= -0.35, P=0.005; r=-0.28, P=0.026; r=-0.30, P=0.019, respectively). Regarding the SOFA scores for each organ, those for the coagulation and neurological components were negatively correlated with the CFH concentration (r=-0.33, P=0.010; r=-0.25, P=0.046, respectively).Conclusion Lower plasma levels of CFH were associated with sepsis severity and mortality and were correlated with the coagulation and neurological components of the SOFA score in patients with sepsis on admission to the ICU.

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“…Data show that the decrease of platelets occur in 35 to 59% of patients with sepsis. It was found that the symbolic risk factor of the death of patients with sepsis is thrombocytopenia (TCP), which is induced by infections, and the recovery of the minimum value of platelet count is associated with the decrease of mortality (5)(6)(7). Studies have shown that when patients are stimulated by endotoxin, platelet activation can be induced by some pathways, which makes platelets play an important role and induce the body to produce an immune response (8,9).…”

Section: Introductionmentioning

confidence: 99%

IL‑18 and IL‑35 in the serum of patients with sepsis thrombocytopenia and the clinical significance

Zhu

Rong

et al. 2019

Exp Ther Med

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Expression levels of interleukin-18 (IL-18) and IL-35 in the serum of patients with sepsis and without thrombocytopenia and patients with sepsis thrombocytopenia (TCP) were detected to preliminarily investigate their clinical significance. One hundred and sixty-six patients admitted to Jinan Central Hospital Affiliated to Shandong University from July 2013 to September 2015 were retrospectively analysed. There were 96 patients with sepsis without thrombocytopenia in the sepsis group, and 70 patients with sepsis TCP in the sepsis TCP group. In the same period, 80 healthy subjects were selected as the control group. Fluorescent quantitative PCR was used for the detection the expression of mRNA levels of IL-18 and IL-35, and Enzyme-linked immunosorbent assay for the detection of the protein concentrations of IL-18 and IL-35 in the serum of peripheral blood. The correlation between IL-18, IL-35 and platelets was analyzed. There were significant differences in albumin, creatinine, total bilirubin and platelet count between the sepsis group and the sepsis TCP group (P<0.05); the expression levels of mRNA of IL-18 and IL-35 in a karyocyte in peripheral blood in the sepsis group and the sepsis TCP group were higher than those in the control group (P<0.05); the expression of mRNA of IL-18 and IL-35 in the sepsis TCP group was higher than those in the sepsis group (P<0.05). The concentration of IL-18 and IL-35 in the sepsis TCP group was higher than in the sepsis group (P<0.05); IL-18 and IL-35 were negatively correlated with platelets (r=-0.8749,-0.6228, P<0.001). There was a significant positive correlation between serum IL-18 and IL-35 in the control group, sepsis group, and sepsis TCP group (r=0.5124, 0.5718, 0.5511, P<0.001). IL-18 and IL-35 were negatively correlated with the reduced degree of platelets in patients with sepsis and are likely to play an important role in the pathogenetic process of sepsis TCP.

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Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

Cited by 35 publications

References 22 publications

Neutrophil Dysfunction in Sepsis

Neutrophil Dysfunction in Sepsis

Association between plasma complement factor H concentration and clinical outcomes in patients with sepsis

IL‑18 and IL‑35 in the serum of patients with sepsis thrombocytopenia and the clinical significance

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