Antibodies in kidney transplantation

Bentall, Andrew John (2015). Antibodies in kidney transplantation. University of Birmingham. M.D.

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The aim of this thesis is to examine the effect of anti-donor antibodies in the clinical management and outcomes of antibody incompatible kidney transplantation. Initial studies were conducted to improve measurement of anti-ABO specific blood group antibodies. The specificity of antibody binding to blood group antigens (BGA) depended upon the assay platform and the nature of the core structure to which the BGA was bound. A standardised haemagglutination assay had excellent reproducibility, which was then applied to the analysis of samples derived from a study of 100 ABO incompatible kidney transplantation (ABOiKTx) in the UK where good clinical outcomes were achieved but there was wide variation reported in local assays quantifying BGA specific antibodies, without survival differences.

In a highly sensitised HLA incompatible kidney transplant recipients (HLAiKTx), I demonstrated long term outcomes were poor compared to a compatible cohort, in particular with pre-formed donor specific anti-HLA Class II antibodies, in which histological injury of antibody damage occurred significantly earlier than with Class I antibodies. Further studies demonstrated that anti-HLA antibodies were associated with an inflammatory phenotype, but anti-donor ABO specific antibodies did not despite the activation of complement. Thus, inhibiting terminal complement activation, whilst reducing early antibody-mediated rejection did not abrogate all inflammation which was associated with the presence of IgM DSA.

Reproducible and standardised assays are needed for antibody assessment in order to make good clinical decisions to improve patient outcomes. Further studies are needed to stop production or block mechanisms of ongoing cellular infiltrate to improve patient outcomes.

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: School of Immunity and Infection
Funders: None/not applicable
Subjects: R Medicine > RC Internal medicine


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