Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the manage...Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophits and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome （SIRS） subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.展开更多
Background: An acute wound infection might be caused by external damage to the skin including abrasions, lacerations, bites, burns, accidents, war injuries and surgical incisions. When a wound fails to heal within a w...Background: An acute wound infection might be caused by external damage to the skin including abrasions, lacerations, bites, burns, accidents, war injuries and surgical incisions. When a wound fails to heal within a week, it should be considered a chronic type. Complement system potent inflammatory cascade in wound infection, is important and altered wound healing. Complement activation leads to the generation of many potent effectors including anaphylatoxin C5a. C5a has induced synthesis of TNF-α and IL-1β in macrophage and monocyte which are all together the goal of the present paper. Methodology: This study was conducted in Al-Kindy and Al-Wasity hospitals in Baghdad on 200 patients suffering from wounds. One hundred patients were with acute wounds infection and the other 100 patients considered as control wounds i.e. without infection. The procedure method was followed according to manufacturer’s instructions (Elabscience, USA) utilizing C5a ELISA kit for conducting the test. Blood samples were taken at 24, 48, 72, 96 and 120 hours of hospitalization of the patients. Results: It was found that the highest concentration of C5a was found at 120 hours after patients hospitalization who were with wound infection, and the mean value of C5a was 4898 pg/ml. 4661 pg/ml of C5a was recorded among patients with acute-phase infection compared to 4387 pg/ml concentration of the same complement among control group without wound infection at 96 hours post residence in hospital. Conclusions: Gram-positive bacteria were more prevalent causing wound infections. Dermacoccus nishinomiyaensis, Kocuria rosea and Kocuria kristinae were isolated for the first time in this locality. A complement 5a (C5a) revealed a very high concentration in acute-phase of wound infections. It was found that C5a was serially elevated with time of hospitalization of wounded and infected patients. C5a was highly elevated with wound infection by Gram-negative bacteria compared to infections by Gram-negatives.展开更多
C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology chara...C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology characterized by accumulation of C3 with absent or scanty immunoglobulin deposition. The keystone defect in both of these pathologies is the unregulated hyperactivity of alternative complement pathway. Specifically, in C3 glomerulopathy patients, there exists a prolongation of C3 cleavage which causes the uncontrolled alternative pathway activation. Many treatments have been investigated for treating C3 glomerulopathy to little or no avail, including calcineurin inhibitors, plasmapharesis, and anti-CD20 monoclonal antibodies. The next logical step is exploring the efficacy of anti-C5 monoclonal antibody therapy in C3 glomerulopathies to target the specific pathophysiology of this particular disease. Eculizumab is an anti-C5 monoclonal antibody that blocks the terminal step of complement activation. This drug has proven to be an effective treatment in other nephrologic pathologies that are caused by complement dysregulation. Here in this paper we discuss and present various case studies and clinical trials available that experiment with Eculizumab in patients with either dense deposit disease or C3 glomerulonephritis. In most of these patients, treatment with Eculizumab has demonstrated clinical and biochemical improvements in kidney function. These results provide encouraging evidence that suggest Eculizumab as a promising therapy for patients with C3 glomerulopathy and warrant that more extensive clinical trials can be designed as a next step.展开更多
文摘Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophits and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome （SIRS） subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.
文摘Background: An acute wound infection might be caused by external damage to the skin including abrasions, lacerations, bites, burns, accidents, war injuries and surgical incisions. When a wound fails to heal within a week, it should be considered a chronic type. Complement system potent inflammatory cascade in wound infection, is important and altered wound healing. Complement activation leads to the generation of many potent effectors including anaphylatoxin C5a. C5a has induced synthesis of TNF-α and IL-1β in macrophage and monocyte which are all together the goal of the present paper. Methodology: This study was conducted in Al-Kindy and Al-Wasity hospitals in Baghdad on 200 patients suffering from wounds. One hundred patients were with acute wounds infection and the other 100 patients considered as control wounds i.e. without infection. The procedure method was followed according to manufacturer’s instructions (Elabscience, USA) utilizing C5a ELISA kit for conducting the test. Blood samples were taken at 24, 48, 72, 96 and 120 hours of hospitalization of the patients. Results: It was found that the highest concentration of C5a was found at 120 hours after patients hospitalization who were with wound infection, and the mean value of C5a was 4898 pg/ml. 4661 pg/ml of C5a was recorded among patients with acute-phase infection compared to 4387 pg/ml concentration of the same complement among control group without wound infection at 96 hours post residence in hospital. Conclusions: Gram-positive bacteria were more prevalent causing wound infections. Dermacoccus nishinomiyaensis, Kocuria rosea and Kocuria kristinae were isolated for the first time in this locality. A complement 5a (C5a) revealed a very high concentration in acute-phase of wound infections. It was found that C5a was serially elevated with time of hospitalization of wounded and infected patients. C5a was highly elevated with wound infection by Gram-negative bacteria compared to infections by Gram-negatives.
文摘C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology characterized by accumulation of C3 with absent or scanty immunoglobulin deposition. The keystone defect in both of these pathologies is the unregulated hyperactivity of alternative complement pathway. Specifically, in C3 glomerulopathy patients, there exists a prolongation of C3 cleavage which causes the uncontrolled alternative pathway activation. Many treatments have been investigated for treating C3 glomerulopathy to little or no avail, including calcineurin inhibitors, plasmapharesis, and anti-CD20 monoclonal antibodies. The next logical step is exploring the efficacy of anti-C5 monoclonal antibody therapy in C3 glomerulopathies to target the specific pathophysiology of this particular disease. Eculizumab is an anti-C5 monoclonal antibody that blocks the terminal step of complement activation. This drug has proven to be an effective treatment in other nephrologic pathologies that are caused by complement dysregulation. Here in this paper we discuss and present various case studies and clinical trials available that experiment with Eculizumab in patients with either dense deposit disease or C3 glomerulonephritis. In most of these patients, treatment with Eculizumab has demonstrated clinical and biochemical improvements in kidney function. These results provide encouraging evidence that suggest Eculizumab as a promising therapy for patients with C3 glomerulopathy and warrant that more extensive clinical trials can be designed as a next step.
