Prognostic immune markers for chronic allograft injury in renal transplant recipients

Jham, Seema Hari (2017). Prognostic immune markers for chronic allograft injury in renal transplant recipients. University of Birmingham. M.D.

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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.

Type of Work: Thesis (Higher Doctorates > M.D.)
Award Type: Higher Doctorates > M.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: Institute of Immunology and Immunotherapy
Funders: None/not applicable
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology > QR180 Immunology


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