Solid Organ Transplantation Rejection

Solid Organ Transplantation Rejection: Types, Mechanisms, and Treatment

• Rejection of a transplanted organ is primarily mediated by activation of alloreactive T cells and antigen-presenting cells such as B lymphocytes.

• Acute allograft rejection is caused primarily by the infiltration of T cells into the allograft, which triggers inflammatory and cytotoxic effects on the graft.

• There are three types of rejection: hyperacute, acute cellular, and chronic rejection.

• Hyperacute rejection is evident within minutes of the transplantation procedure when preformed donor-specific antibodies are present in the recipient at the time of the transplant.

• Acute cellular rejection (ACR) is the most common type and is mediated by alloreactive T-lymphocytes. Biopsy of the allograft is often used to guide therapy.

• Antibody-mediated rejection (AMR) is characterized by the presence of antibodies directed against donor vascular endothelium. Antibodies activate complement, which creates a membrane attack complex that directly damages the organ.

• Chronic rejection is a major cause of graft loss and presents as a slow and indolent form of ACR, in which the involvement of the humoral immune system and antibodies against the vascular endothelium appear to play a role.

• The primary goal of acute rejection therapy is to minimize the intensity of the immune response and prevent irreversible injury to the allograft.

• Treatment of ACR includes optimizing immunosuppression, increasing the doses of current immunosuppressive drugs, pulse corticosteroids, or short-term treatment with a polyclonal or monoclonal antibody.

• Treatment of AMR involves removing existing antibodies through plasmapheresis or intravenous immunoglobulin (IVIG) and inhibiting their re-development through rituximab, bortezomib, or eculizumab.

• Plasmapheresis is a procedure in which the plasma in the patient's blood is removed and replaced with another fluid, similar to what happens in kidney dialysis.

• Rituximab is a chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes and has been shown to improve graft survival in combination with plasmapheresis and IVIG in patients with AMR.The Use of Eculizumab in Renal Transplantation: Overview, Treatment of AMR, and Re-start Prophylaxis

• Eculizumab is primarily used in renal transplantation to treat atypical hemolytic-uremic syndrome (aHUS) and antibody-mediated rejection (AMR) post-transplant.

• Eculizumab inhibits the cleavage of C5, thus preventing the formation of inflammatory molecules C5a and C5b, including membrane attack complex (MAC).

• Eculizumab appears effective in protecting renal allografts when post-transplant aHUS or AMR occurs, but published cases have relatively short follow-up.

• Patients should receive vaccination against Neisseria meningitidis before receiving eculizumab.

• A retrospective observational study showed that eculizumab treatment for early post-transplant AMR increased the median estimated glomerular filtration rate from 21 to 34 mL/min within a week.

• Only 16.7% of biopsied patients had persistent active AMR within 4-6 months, and no graft losses occurred.

• Larger trials are needed to evaluate the efficacy of eculizumab in treating AMR.

• Prophylactic agents, such as valganciclovir, nystatin, trimethoprim-sulfamethoxazole, and H2-receptor antagonists or proton-pump inhibitors, may be added to minimize adverse effects associated with intensive immunosuppression regimens.

• Valganciclovir is used to prevent cytomegalovirus infection, nystatin for fungal infections, and trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia and urinary tract infections.

• H2-receptor antagonists or proton-pump inhibitors are used to prevent gastric ulcers caused by immunosuppressive drugs.

• The use of prophylactic agents should be re-evaluated and restarted as necessary, particularly when immunosuppression is increased or changed.

• For questions, contact [email protected].

Solid Organ Transplantation Rejection: Types, Mechanisms, and Treatment

• Rejection of a transplanted organ is primarily mediated by activation of alloreactive T cells and antigen-presenting cells such as B lymphocytes.

• Acute allograft rejection is caused primarily by the infiltration of T cells into the allograft, which triggers inflammatory and cytotoxic effects on the graft.

• There are three types of rejection: hyperacute, acute cellular, and chronic rejection.

• Hyperacute rejection is evident within minutes of the transplantation procedure when preformed donor-specific antibodies are present in the recipient at the time of the transplant.

• Acute cellular rejection (ACR) is the most common type and is mediated by alloreactive T-lymphocytes. Biopsy of the allograft is often used to guide therapy.

• Antibody-mediated rejection (AMR) is characterized by the presence of antibodies directed against donor vascular endothelium. Antibodies activate complement, which creates a membrane attack complex that directly damages the organ.

• Chronic rejection is a major cause of graft loss and presents as a slow and indolent form of ACR, in which the involvement of the humoral immune system and antibodies against the vascular endothelium appear to play a role.

• The primary goal of acute rejection therapy is to minimize the intensity of the immune response and prevent irreversible injury to the allograft.

• Treatment of ACR includes optimizing immunosuppression, increasing the doses of current immunosuppressive drugs, pulse corticosteroids, or short-term treatment with a polyclonal or monoclonal antibody.

• Treatment of AMR involves removing existing antibodies through plasmapheresis or intravenous immunoglobulin (IVIG) and inhibiting their re-development through rituximab, bortezomib, or eculizumab.

• Plasmapheresis is a procedure in which the plasma in the patient's blood is removed and replaced with another fluid, similar to what happens in kidney dialysis.

• Rituximab is a chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes and has been shown to improve graft survival in combination with plasmapheresis and IVIG in patients with AMR.The Use of Eculizumab in Renal Transplantation: Overview, Treatment of AMR, and Re-start Prophylaxis

• Eculizumab is primarily used in renal transplantation to treat atypical hemolytic-uremic syndrome (aHUS) and antibody-mediated rejection (AMR) post-transplant.

• Eculizumab inhibits the cleavage of C5, thus preventing the formation of inflammatory molecules C5a and C5b, including membrane attack complex (MAC).

• Eculizumab appears effective in protecting renal allografts when post-transplant aHUS or AMR occurs, but published cases have relatively short follow-up.

• Patients should receive vaccination against Neisseria meningitidis before receiving eculizumab.

• A retrospective observational study showed that eculizumab treatment for early post-transplant AMR increased the median estimated glomerular filtration rate from 21 to 34 mL/min within a week.

• Only 16.7% of biopsied patients had persistent active AMR within 4-6 months, and no graft losses occurred.

• Larger trials are needed to evaluate the efficacy of eculizumab in treating AMR.

• Prophylactic agents, such as valganciclovir, nystatin, trimethoprim-sulfamethoxazole, and H2-receptor antagonists or proton-pump inhibitors, may be added to minimize adverse effects associated with intensive immunosuppression regimens.

• Valganciclovir is used to prevent cytomegalovirus infection, nystatin for fungal infections, and trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia and urinary tract infections.

• H2-receptor antagonists or proton-pump inhibitors are used to prevent gastric ulcers caused by immunosuppressive drugs.

• The use of prophylactic agents should be re-evaluated and restarted as necessary, particularly when immunosuppression is increased or changed.

• For questions, contact [email protected].

Solid Organ Transplantation Rejection: Types, Mechanisms, and Treatment

• Rejection of a transplanted organ is primarily mediated by activation of alloreactive T cells and antigen-presenting cells such as B lymphocytes.

• Acute allograft rejection is caused primarily by the infiltration of T cells into the allograft, which triggers inflammatory and cytotoxic effects on the graft.

• There are three types of rejection: hyperacute, acute cellular, and chronic rejection.

• Hyperacute rejection is evident within minutes of the transplantation procedure when preformed donor-specific antibodies are present in the recipient at the time of the transplant.

• Acute cellular rejection (ACR) is the most common type and is mediated by alloreactive T-lymphocytes. Biopsy of the allograft is often used to guide therapy.

• Antibody-mediated rejection (AMR) is characterized by the presence of antibodies directed against donor vascular endothelium. Antibodies activate complement, which creates a membrane attack complex that directly damages the organ.

• Chronic rejection is a major cause of graft loss and presents as a slow and indolent form of ACR, in which the involvement of the humoral immune system and antibodies against the vascular endothelium appear to play a role.

• The primary goal of acute rejection therapy is to minimize the intensity of the immune response and prevent irreversible injury to the allograft.

• Treatment of ACR includes optimizing immunosuppression, increasing the doses of current immunosuppressive drugs, pulse corticosteroids, or short-term treatment with a polyclonal or monoclonal antibody.

• Treatment of AMR involves removing existing antibodies through plasmapheresis or intravenous immunoglobulin (IVIG) and inhibiting their re-development through rituximab, bortezomib, or eculizumab.

• Plasmapheresis is a procedure in which the plasma in the patient's blood is removed and replaced with another fluid, similar to what happens in kidney dialysis.

• Rituximab is a chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes and has been shown to improve graft survival in combination with plasmapheresis and IVIG in patients with AMR.The Use of Eculizumab in Renal Transplantation: Overview, Treatment of AMR, and Re-start Prophylaxis

• Eculizumab is primarily used in renal transplantation to treat atypical hemolytic-uremic syndrome (aHUS) and antibody-mediated rejection (AMR) post-transplant.

• Eculizumab inhibits the cleavage of C5, thus preventing the formation of inflammatory molecules C5a and C5b, including membrane attack complex (MAC).

• Eculizumab appears effective in protecting renal allografts when post-transplant aHUS or AMR occurs, but published cases have relatively short follow-up.

• Patients should receive vaccination against Neisseria meningitidis before receiving eculizumab.

• A retrospective observational study showed that eculizumab treatment for early post-transplant AMR increased the median estimated glomerular filtration rate from 21 to 34 mL/min within a week.

• Only 16.7% of biopsied patients had persistent active AMR within 4-6 months, and no graft losses occurred.

• Larger trials are needed to evaluate the efficacy of eculizumab in treating AMR.

• Prophylactic agents, such as valganciclovir, nystatin, trimethoprim-sulfamethoxazole, and H2-receptor antagonists or proton-pump inhibitors, may be added to minimize adverse effects associated with intensive immunosuppression regimens.

• Valganciclovir is used to prevent cytomegalovirus infection, nystatin for fungal infections, and trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia and urinary tract infections.

• H2-receptor antagonists or proton-pump inhibitors are used to prevent gastric ulcers caused by immunosuppressive drugs.

• The use of prophylactic agents should be re-evaluated and restarted as necessary, particularly when immunosuppression is increased or changed.

• For questions, contact [email protected].

Solid Organ Transplantation Rejection: Types, Mechanisms, and Treatment

• Rejection of a transplanted organ is primarily mediated by activation of alloreactive T cells and antigen-presenting cells such as B lymphocytes.

• Acute allograft rejection is caused primarily by the infiltration of T cells into the allograft, which triggers inflammatory and cytotoxic effects on the graft.

• There are three types of rejection: hyperacute, acute cellular, and chronic rejection.

• Hyperacute rejection is evident within minutes of the transplantation procedure when preformed donor-specific antibodies are present in the recipient at the time of the transplant.

• Acute cellular rejection (ACR) is the most common type and is mediated by alloreactive T-lymphocytes. Biopsy of the allograft is often used to guide therapy.

• Antibody-mediated rejection (AMR) is characterized by the presence of antibodies directed against donor vascular endothelium. Antibodies activate complement, which creates a membrane attack complex that directly damages the organ.

• Chronic rejection is a major cause of graft loss and presents as a slow and indolent form of ACR, in which the involvement of the humoral immune system and antibodies against the vascular endothelium appear to play a role.

• The primary goal of acute rejection therapy is to minimize the intensity of the immune response and prevent irreversible injury to the allograft.

• Treatment of ACR includes optimizing immunosuppression, increasing the doses of current immunosuppressive drugs, pulse corticosteroids, or short-term treatment with a polyclonal or monoclonal antibody.

• Treatment of AMR involves removing existing antibodies through plasmapheresis or intravenous immunoglobulin (IVIG) and inhibiting their re-development through rituximab, bortezomib, or eculizumab.

• Plasmapheresis is a procedure in which the plasma in the patient's blood is removed and replaced with another fluid, similar to what happens in kidney dialysis.

• Rituximab is a chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes and has been shown to improve graft survival in combination with plasmapheresis and IVIG in patients with AMR.The Use of Eculizumab in Renal Transplantation: Overview, Treatment of AMR, and Re-start Prophylaxis

• Eculizumab is primarily used in renal transplantation to treat atypical hemolytic-uremic syndrome (aHUS) and antibody-mediated rejection (AMR) post-transplant.

• Eculizumab inhibits the cleavage of C5, thus preventing the formation of inflammatory molecules C5a and C5b, including membrane attack complex (MAC).

• Eculizumab appears effective in protecting renal allografts when post-transplant aHUS or AMR occurs, but published cases have relatively short follow-up.

• Patients should receive vaccination against Neisseria meningitidis before receiving eculizumab.

• A retrospective observational study showed that eculizumab treatment for early post-transplant AMR increased the median estimated glomerular filtration rate from 21 to 34 mL/min within a week.

• Only 16.7% of biopsied patients had persistent active AMR within 4-6 months, and no graft losses occurred.

• Larger trials are needed to evaluate the efficacy of eculizumab in treating AMR.

• Prophylactic agents, such as valganciclovir, nystatin, trimethoprim-sulfamethoxazole, and H2-receptor antagonists or proton-pump inhibitors, may be added to minimize adverse effects associated with intensive immunosuppression regimens.

• Valganciclovir is used to prevent cytomegalovirus infection, nystatin for fungal infections, and trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia and urinary tract infections.

• H2-receptor antagonists or proton-pump inhibitors are used to prevent gastric ulcers caused by immunosuppressive drugs.

• The use of prophylactic agents should be re-evaluated and restarted as necessary, particularly when immunosuppression is increased or changed.

• For questions, contact [email protected].