Prognostic immune markers for chronic allograft injury inrenal transplant recipients

[摘要] Introduction: Alloimmunity is a major contributor to chronic allograft injury. There are currently no routine clinical cell-based assays that allow quantification of the recipients'alloimmune response towards a graft. Previous work from our group identified indirect alloimmune responses to non-polymorphic regions of HLA Class 1. The aim of this thesis was to assess the alloimmune response in renal transplant recipients (RTRs) by using synthetic peptides to non­polymorphic regions ofHLA Class 2. Methods: Responses to newly synthesized HLA Class 2 peptides were tested in RTRs via any­ interferon ELISPOT assay. Cell surface staining techniques and Luminex technology were used to identify the T-cell subsets driving the immune responses and subsequent cytokine production respectively. Results: Increased responses to HLA Class 2 derived peptides were detected in renal transplant recipients compared to healthy controls. The activated effector memory subset ofT-cells was expanded in RTRs compared to healthy controls and generated these responses. T effector memory cell dependent TNF-a and IL-2 and T regulatory dependent IL-10 synthesis in the presence of specific peptide antigen was detected. Conclusion: A potential reproducible assay ofT cell alloreactivity has been identified to help stratify RTRs at risk of an ongoing alloimmune response but needs further testing in a larger multicentre study.

[发布机构] University:University of Birmingham;Department:Institute of Immunology and Immunotherapy

[关键词] Q Science;QH Natural history;QH301 Biology