Background and Aims:Cirrhosis patients exhibit cyto-penia,and,at times refractory neutropenia to granulocyte colony-stimulating factor(G-CSF),which acts through the CSF3-receptor(CSF3R),and changes in CSF3R can affect...Background and Aims:Cirrhosis patients exhibit cyto-penia,and,at times refractory neutropenia to granulocyte colony-stimulating factor(G-CSF),which acts through the CSF3-receptor(CSF3R),and changes in CSF3R can affect the response.We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients.Methods:Cirrhotic patients(n=127)and controls(n=26)with clini-cally indicated bone marrow(BM)examination were stud-ied.BM assessment was done by qRT-PCR and immunohis-tochemistry(IHC)for CSF3R.Circulating G-CSF,CSF3R,and carcinoembryonic antigen cell adhesion molecule-1(CEACAM1)were measured.BM hematopoietic precursor cells and their alterations were examined by flow cytom-etry.The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia.Results:The mean age was 48.6±13.4 years,and 80.3%were men.Circulatory CSF3R reduction was noted with the advance-ment of cirrhosis,and confirmed by qRT-PCR and IHC in BM.CSF3R decline was related to decreased hematopoietic stem cells(HSCs)and downregulation of CSF3R in the re-maining HSCs.Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation.Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up.Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia.Conclu-sions:Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circula-tion,making patients prone to infection and inadequate response to exogenous G-CSF.展开更多
文摘Background and Aims:Cirrhosis patients exhibit cyto-penia,and,at times refractory neutropenia to granulocyte colony-stimulating factor(G-CSF),which acts through the CSF3-receptor(CSF3R),and changes in CSF3R can affect the response.We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients.Methods:Cirrhotic patients(n=127)and controls(n=26)with clini-cally indicated bone marrow(BM)examination were stud-ied.BM assessment was done by qRT-PCR and immunohis-tochemistry(IHC)for CSF3R.Circulating G-CSF,CSF3R,and carcinoembryonic antigen cell adhesion molecule-1(CEACAM1)were measured.BM hematopoietic precursor cells and their alterations were examined by flow cytom-etry.The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia.Results:The mean age was 48.6±13.4 years,and 80.3%were men.Circulatory CSF3R reduction was noted with the advance-ment of cirrhosis,and confirmed by qRT-PCR and IHC in BM.CSF3R decline was related to decreased hematopoietic stem cells(HSCs)and downregulation of CSF3R in the re-maining HSCs.Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation.Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up.Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia.Conclu-sions:Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circula-tion,making patients prone to infection and inadequate response to exogenous G-CSF.
