The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks sti...The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice.While hepatocyte transplantation may be effectively correct metabolic defects,it is far less effective in restoring liver function than liver transplantation.Tissue engineering,using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells,holds great promise for the treatment of failure of organs within gastrointestinal tract,such as endstage liver disease,pancreatic insufficiency,bowel failure and type 1 diabetes.Particularly in the liver field,where there is a significant mortality of patients awaiting transplant,human bioengineering may offer a source of readily available organs for transplantation.The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.展开更多
Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries.Recurrent hepatitis C infection of the allograft is universal and immediate followin...Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries.Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation,being associated with accelerated progression to cirrhosis,graft loss and death.Graft and patient survival is reduced in liver transplant recipients with recurrent Hepatitis C virus(HCV) infection compared to HCV-negative recipients.Many variables may impact on recurrent HCV liver disease.Overall,excess immunosuppression is believed to be a key factor;however,no immunosuppressive regimen has been identified to be more beneficial or less harmful.Donor age limitations,exclusion of moderately to severely steatotic livers and minimization of ischemic times could be a potential strategy to minimize the severity of HCV disease in transplanted subjects.After transplantation,antiviral therapy based on pegylated IFN alpha with or without ribavirin is associated with far less results than that reported for immunocompetent HCV-infected patients.New findings in the field of immunotherapy and genomic medicine applied to this context are promising.展开更多
Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of pr...Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis.In the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome.Serum,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood donors.The level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of controls.By immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the controls.In conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome.The presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.展开更多
文摘The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice.While hepatocyte transplantation may be effectively correct metabolic defects,it is far less effective in restoring liver function than liver transplantation.Tissue engineering,using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells,holds great promise for the treatment of failure of organs within gastrointestinal tract,such as endstage liver disease,pancreatic insufficiency,bowel failure and type 1 diabetes.Particularly in the liver field,where there is a significant mortality of patients awaiting transplant,human bioengineering may offer a source of readily available organs for transplantation.The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.
文摘Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries.Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation,being associated with accelerated progression to cirrhosis,graft loss and death.Graft and patient survival is reduced in liver transplant recipients with recurrent Hepatitis C virus(HCV) infection compared to HCV-negative recipients.Many variables may impact on recurrent HCV liver disease.Overall,excess immunosuppression is believed to be a key factor;however,no immunosuppressive regimen has been identified to be more beneficial or less harmful.Donor age limitations,exclusion of moderately to severely steatotic livers and minimization of ischemic times could be a potential strategy to minimize the severity of HCV disease in transplanted subjects.After transplantation,antiviral therapy based on pegylated IFN alpha with or without ribavirin is associated with far less results than that reported for immunocompetent HCV-infected patients.New findings in the field of immunotherapy and genomic medicine applied to this context are promising.
文摘Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis.In the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome.Serum,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood donors.The level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of controls.By immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the controls.In conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome.The presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.
