BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neut...BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical settings.AIM To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of CRS-1.METHODS We performed a retrospective cohort,multi-centre study.From January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary syndrome.We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.RESULTS Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required dialysis.Neither the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak value.Finally,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly correlated.CONCLUSION In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart disease.So,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.展开更多
Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by ...Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)cells.Thus far,the absence of markers that uniquely identify DC-10 has limited in vivo studies.By in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for DC-10.The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood.CD14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of IL-12.Moreover,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 cells.Finally,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic signature.These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10.These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.展开更多
文摘BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical settings.AIM To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of CRS-1.METHODS We performed a retrospective cohort,multi-centre study.From January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary syndrome.We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.RESULTS Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required dialysis.Neither the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak value.Finally,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly correlated.CONCLUSION In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart disease.So,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.
基金This work was supported by research funding from the Italian Telethon Foundation(TGT17G01)the Italian Assodation for Cancer Research,IG-18540,AIRC 2016 to S.G.+1 种基金by COST Action BM1305 A-FAACT(http://www.afactt.eu)and COST Action BM1404 Mye EUNITER(http://www.mye euniter.eu)COST is supported by the EU Framework Program Horizon 2020.MJ.U.was supported by the NSF Graduate Research Fellowship Grant#DGE-1147470.
文摘Tolerogenic dendritic cells(DCs)are key players in maintaining immunological homeostasis,dampening immune responses,and promoting tolerance.DC-10,a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4,play a pivotal role in promoting tolerance via T regulatory type 1(Tr1)cells.Thus far,the absence of markers that uniquely identify DC-10 has limited in vivo studies.By in vitro gene expression profiling of differentiated human DCs,we identified CD141 and CD163 as surface markers for DC-10.The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood.CD14+CD16+CD141+CD163+cells isolated from the peripheral blood of healthy subjects(ex vivo DC-10)produced spontaneously and upon activation of IL-10 and limited levels of IL-12.Moreover,in vitro stimulation of allogeneic naive CD4+T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+Tr1 cells.Finally,ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile,which are characterized by an anti-inflammatory and pro-tolerogenic signature.These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10.These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.
