Research Topic

Assessing Functional Immune Responses after Pediatric Liver Transplantation – Opportunities for Individualization of Therapy and Improvement of Graft Outcome

About this Research Topic

Solid organ transplantation represents a major challenge for the host immune system. Implantation of a liver allograft triggers complex immune reactions that contribute to a fragile balance between tolerance and rejection. Direct allorecognition of donor HLA antigen is translated into the cytotoxic activity seen in acute cellular rejection, while indirect allorecognition of donor antigens can fuel either rejection or tolerance of the graft depending on co-stimulatory influences. Immune response after transplantation occurs immediately after reperfusion, with specific and dynamic adaptive changes that follow a characteristic pattern over the first few days. Most patients subsequently seem to achieve certain stability in immune patterns. However, immunological events such as acute cellular rejection leave their marks, and at 12 months after transplantation, liver transplanted children in stable condition display different immune marker profiles of Th1 and Th2 derived cytokines in correspondence with a history of rejection.

While acute cellular rejection represents a major risk for organ survival, risks of over-immunosuppression such as infection, malignancy, and drug toxicity account for 25% of deaths during the long-term follow-up after liver transplantation. The clinical challenge of “getting it right”, i.e. of achieving the fine balance between over- and under-immunosuppression for any individual patient, to this day, is aggravated by the lack of reliable biomarkers that indicate a clear need for more immunosuppression or identify those suitable for withdrawal of immunosuppressive therapy. In children, in particular, the impact of a maturing immune system on the adaptation to the immunological assault of transplantation is incompletely understood.

This Research Topic aims to foster the understanding of immune reactions following liver transplantation in childhood, with a particular focus on functional immune status and its impact on the clinical course. We welcome submissions of Original Research, Review, Mini Review articles, and Methods articles focusing on the following subtopics:

1) Patterns of immune responses after transplantation – impact of individual immune phenotypes vs demographic and clinical factors
2) New markers to predict and diagnose acute cellular rejection
3) New statistical methods to assess immune responses over time
4) Understanding the interplay of functional immune status, pharmacokinetic data, and clinical outcome
5) Impact of the maturing immune system on the immune response to pediatric liver transplantation
6) Studies on the immunological and clinical significance of donor-specific antibodies (DSAs) in liver transplanted children


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Solid organ transplantation represents a major challenge for the host immune system. Implantation of a liver allograft triggers complex immune reactions that contribute to a fragile balance between tolerance and rejection. Direct allorecognition of donor HLA antigen is translated into the cytotoxic activity seen in acute cellular rejection, while indirect allorecognition of donor antigens can fuel either rejection or tolerance of the graft depending on co-stimulatory influences. Immune response after transplantation occurs immediately after reperfusion, with specific and dynamic adaptive changes that follow a characteristic pattern over the first few days. Most patients subsequently seem to achieve certain stability in immune patterns. However, immunological events such as acute cellular rejection leave their marks, and at 12 months after transplantation, liver transplanted children in stable condition display different immune marker profiles of Th1 and Th2 derived cytokines in correspondence with a history of rejection.

While acute cellular rejection represents a major risk for organ survival, risks of over-immunosuppression such as infection, malignancy, and drug toxicity account for 25% of deaths during the long-term follow-up after liver transplantation. The clinical challenge of “getting it right”, i.e. of achieving the fine balance between over- and under-immunosuppression for any individual patient, to this day, is aggravated by the lack of reliable biomarkers that indicate a clear need for more immunosuppression or identify those suitable for withdrawal of immunosuppressive therapy. In children, in particular, the impact of a maturing immune system on the adaptation to the immunological assault of transplantation is incompletely understood.

This Research Topic aims to foster the understanding of immune reactions following liver transplantation in childhood, with a particular focus on functional immune status and its impact on the clinical course. We welcome submissions of Original Research, Review, Mini Review articles, and Methods articles focusing on the following subtopics:

1) Patterns of immune responses after transplantation – impact of individual immune phenotypes vs demographic and clinical factors
2) New markers to predict and diagnose acute cellular rejection
3) New statistical methods to assess immune responses over time
4) Understanding the interplay of functional immune status, pharmacokinetic data, and clinical outcome
5) Impact of the maturing immune system on the immune response to pediatric liver transplantation
6) Studies on the immunological and clinical significance of donor-specific antibodies (DSAs) in liver transplanted children


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 March 2021 Abstract
31 July 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 March 2021 Abstract
31 July 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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