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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Abstract

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.

Supervisor(s):