State of the art on the research for biomarkers allowing individual, tailor-made minimization of immunosuppression

Sawitzki, Birgit; Reinke, Petra; Pascher, Andreas; Volk, Hans‐Dieter

doi:10.1097/mot.0b013e32834066b0

Cited by 13 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the monitoring of CD4 + lymphocyte adenosine triphosphate levels has been suggested as an alternative means of assessing the net state of immunosuppression,10 although others have suggested that the utility of this assay is its ability to better identify recipients who are more susceptible to infection‐related complications 11. Clearly, specific and meaningful biomarkers are needed to assess individual risks for immunological complications 12, 13. Although immunosuppression minimization has been shown to reduce the complications of chronic immunosuppression,14, 15 only a minority of LT recipients are able to achieve complete withdrawal,16 and this means that the majority of patients likely will remain on chronic immunosuppression for their entire lives.…”

Section: Concepts In Immunosuppressionmentioning

confidence: 99%

Present state of immunosuppressive therapy in liver transplant recipients

2011

View full text Add to dashboard Cite

Key Points 1. Our increasing understanding of the signaling pathways and cellular interactions in transplant immunobiology has facilitated targeted strategies using novel immunosuppressive agents. 2. The pattern of immunosuppressive drug use in the United States continues to change, and the changes include the use of antibody induction therapy and the agents used in maintenance therapy. 3. The driving forces behind the development of new immunosuppressive regimens are the long-term complications of current immunosuppressive regimens (particularly renal dysfunction and metabolic disturbances). Liver Transpl 17:S1-S9, 2011. V C 2011 AASLD.Received July 27, 2011; accepted August 9, 2011.Recent advances in molecular and cellular immunology have further unraveled the interactions between antigen-presenting cells (APCs), T cells, and B cells. These advances include the elucidation of pathways involved in T cell activation and apoptosis, the identification of novel regulatory cells (including T regulatory cells and suppressive APCs), and a greater appreciation of the complex interactions between innate and adaptive immunity. Furthermore, the elucidation of the triggers of B cell activation and antibody synthesis has allowed the development of B cell-specific immunosuppression, although the impact of donor-specific antibodies and B cells on liver transplantation (LT) is still being assessed. Nevertheless, the focus of immunosuppressive drug development has continued to be the T cell. Thus, we briefly review our current understanding of T cell activation and proliferation as well as the mechanisms of action of immunosuppressive agents.

show abstract

Section: Concepts In Immunosuppressionmentioning

confidence: 99%

Present state of immunosuppressive therapy in liver transplant recipients

2011

View full text Add to dashboard Cite

show abstract

“…They have shown therapeutic effects in treating autoimmune disease such as type 1 diabetes (T1D) [9, 10•, 11••, 12], GvHD after hematopoietic stem cell transplantation (HSC) [8, 13•, 14••, 15] and also preventing rejection of solid organ transplants [3,7,16]. In some studies, higher proportions of Tregs or certain subsets were detected in the peripheral blood of Boperationally tolerant^patients [17,18] with their frequencies or numbers being reduced in some patients experiencing rejection [18,19]. In addition, Tregs can impose regulatory function onto conventional alloreactive T cells in a process now being known as infectious tolerance [16,20].…”

Section: Introductionmentioning

confidence: 99%

Treg Therapy in Transplantation: How and When Will We Do It?

Niemann

Sawitzki

2015

Curr Transpl Rep

Self Cite

View full text Add to dashboard Cite

Adoptive therapy with regulatory T cells (Tregs) has shown great promises in many experimental models to induce permanent graft acceptance and tolerance to alloantigens. However, although their tolerogenic therapeutic potential has been demonstrated in clinical hematopoietic stem cell transplantation and partially in patients with early onset type I diabetes, translation into clinical testing for solid organ transplantation is still lacking or only slowly starting. This is in part due to the fact that many questions regarding not only the optimal type of Tregs but also the best-suited clinical trial design are unsolved and highly debated within the scientific community. With facilities for purifying and expanding Tregs and the clinical trials being very expensive, these points should be carefully discussed. Here, we summarized recent results regarding adoptive Treg therapy in solid organ transplantation additionally addressing the above-mentioned questions.

show abstract

“…Thus, modern transplantation medicine is moving away from the exploration of novel immunosuppressive agents toward the induction of allograft tolerance in organ recipients. It causes a pressing need to search for unique tolerance biomarkers as surrogate endpoints of immunosuppressive strategies, or measures for predicting successful tolerance induction [2, 3]. Recipients with graft tolerance retain well-functioning grafts after cessation of immunosuppressive regimens, referred to as operational tolerance [4].…”

Section: Introductionmentioning

confidence: 99%

Recipients withIn UteroInduction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin

Chen

et al. 2014

Disease Markers

View full text Add to dashboard Cite

The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2Kb in engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance.

show abstract

State of the art on the research for biomarkers allowing individual, tailor-made minimization of immunosuppression

Cited by 13 publications

References 45 publications

Present state of immunosuppressive therapy in liver transplant recipients

Present state of immunosuppressive therapy in liver transplant recipients

Treg Therapy in Transplantation: How and When Will We Do It?

Recipients withIn UteroInduction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin

Contact Info

Product

Resources

About