The use of marginal organs currently represents a major issue in organ transplantation. Approximately, one-third of the deceased donor organs originate in Europe from = 60-year-old donors, and the advanced donor age is the factor with the strongest negative impact on outcome in kidney transplantation. Recipients of marginal organs are considered 'high immunological risk' as these organs are extremely vulnerable to immune attack due to high alloantigen expression and diminished number of functional tissue units. Therefore, these patients generally receive more potent immunosuppression, including induction therapy with anti-T cell agents. However, it is a matter of debate whether this is indeed necessary in all organs.
This Research Topic will shed light on the definition of immunological risk constellations, molecular events that lead to a higher immunogenicity and higher incidence of rejection, delayed graft function (DGF) and impaired survival of marginal organs, and therapeutic and organizational measures to prevent an inferior clinical outcome in recipients of such organs. Explaining the higher immunogenicity of marginal organs, increased MHC expression was demonstrated in mice with ischemia-caused acute tubular necrosis of the kidney. In intestinal ischemia and reperfusion injury (IRI), treatment with anti-thymocyte globulin (ATG) led to reduced local infiltration of T-lymphocytes to the tissue with less inflammation, chemotaxis and apoptosis. Besides a prolonged ischemia time of the organ, the pre-transplant presence of HLA antibodies in the recipient is one of the main risk factors for DGF, most probably due to a higher incidence of subclinical antibody-mediated rejection. The impact of DGF on graft survival is stronger in patients with HLA antibodies. The role of non-HLA alloimmunity has not been addressed in this context although the expression of MIC-A alloantigens is higher on stressed tissue. Highly sensitized patients demonstrate a higher incidence of DGF, which can strongly be reduced by induction therapy with ATG. Even elderly recipients who receive marginal organs are at a higher risk of immunological rejection, indicating not thoroughly clarified interactions between a marginal donor organ, IRI, T and B cell-mediated rejection and occurrence of adverse clinical events.
We welcome the submission of Review and Original Research articles, Opinion and Perspective covering, but not limited to, the following immunological aspects:
1. Molecular mechanisms of organ aging.
2. Transplantation of pre-sensitized patients with marginal kidneys, livers, hearts, lungs, pancreata and intestine.
3. Role of HLA and non-HLA immunity (excluding innate immunity) in transplantation of patients with marginal organs.
4. Clinical and experimental studies on immunosuppression in recipients of marginal kidneys, livers, hearts, lungs, pancreata and intestine.
5. Conservation, machine perfusion and pre-conditioning of marginal organs to diminish their antigenicity and vulnerability.
6. Molecular mechanisms and microscopic features of DGF and IRI.
7. Antigen silencing of organs by experimental intervention to prevent immunological rejection.
8. 'Old-to-old' versus 'old-to-younger' organ allocation and immunological consequences.
9. Usage of donor/patient immunological risk indices for allocation of marginal organs.
10. Use of pancreata from older donors and immunological outcome.
The use of marginal organs currently represents a major issue in organ transplantation. Approximately, one-third of the deceased donor organs originate in Europe from = 60-year-old donors, and the advanced donor age is the factor with the strongest negative impact on outcome in kidney transplantation. Recipients of marginal organs are considered 'high immunological risk' as these organs are extremely vulnerable to immune attack due to high alloantigen expression and diminished number of functional tissue units. Therefore, these patients generally receive more potent immunosuppression, including induction therapy with anti-T cell agents. However, it is a matter of debate whether this is indeed necessary in all organs.
This Research Topic will shed light on the definition of immunological risk constellations, molecular events that lead to a higher immunogenicity and higher incidence of rejection, delayed graft function (DGF) and impaired survival of marginal organs, and therapeutic and organizational measures to prevent an inferior clinical outcome in recipients of such organs. Explaining the higher immunogenicity of marginal organs, increased MHC expression was demonstrated in mice with ischemia-caused acute tubular necrosis of the kidney. In intestinal ischemia and reperfusion injury (IRI), treatment with anti-thymocyte globulin (ATG) led to reduced local infiltration of T-lymphocytes to the tissue with less inflammation, chemotaxis and apoptosis. Besides a prolonged ischemia time of the organ, the pre-transplant presence of HLA antibodies in the recipient is one of the main risk factors for DGF, most probably due to a higher incidence of subclinical antibody-mediated rejection. The impact of DGF on graft survival is stronger in patients with HLA antibodies. The role of non-HLA alloimmunity has not been addressed in this context although the expression of MIC-A alloantigens is higher on stressed tissue. Highly sensitized patients demonstrate a higher incidence of DGF, which can strongly be reduced by induction therapy with ATG. Even elderly recipients who receive marginal organs are at a higher risk of immunological rejection, indicating not thoroughly clarified interactions between a marginal donor organ, IRI, T and B cell-mediated rejection and occurrence of adverse clinical events.
We welcome the submission of Review and Original Research articles, Opinion and Perspective covering, but not limited to, the following immunological aspects:
1. Molecular mechanisms of organ aging.
2. Transplantation of pre-sensitized patients with marginal kidneys, livers, hearts, lungs, pancreata and intestine.
3. Role of HLA and non-HLA immunity (excluding innate immunity) in transplantation of patients with marginal organs.
4. Clinical and experimental studies on immunosuppression in recipients of marginal kidneys, livers, hearts, lungs, pancreata and intestine.
5. Conservation, machine perfusion and pre-conditioning of marginal organs to diminish their antigenicity and vulnerability.
6. Molecular mechanisms and microscopic features of DGF and IRI.
7. Antigen silencing of organs by experimental intervention to prevent immunological rejection.
8. 'Old-to-old' versus 'old-to-younger' organ allocation and immunological consequences.
9. Usage of donor/patient immunological risk indices for allocation of marginal organs.
10. Use of pancreata from older donors and immunological outcome.