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Mengsha Hu

Alloantibodies against human leukocyte antigens (HLA) develop in response to transplantation, pregnancy and blood transfusions. Their presence may preclude transplantation from proceeding, whereas their development after kidney, pancreas, heart and lung transplantation is a major cause of graft loss. Although a number of conventional techniques are used clinically to identify and characterise HLA alloantibody in patient sera, significant uncertainty exists regarding the pathogenic potential of alloantibodies detected with currently available techniques and there is not a clinically applicable assay to assess the binding kinetics of alloantibody and donor HLA targets directly in patient sera.

These all limit our ability to assess the immunological risk associated with a particular transplant and to intervene early before irreversible graft injury is established.

The detection of interactions between biomolecules in complex mixtures, such as patient sera is challenging with present biophysical techniques, which fundamentally arises from the polydisperse and heterogeneous nature of human sera and the significantly low alloantibody concentration. To overcome these problems, I aim to implement and improve a microfluidic spatio-temporal diffusion-based platform that is capable of characterising protein-protein interactions under native conditions in the condensed phase, and apply this technology to investigate, in a sensitive and quantitative manner, interactions between HLA and alloantibodies. I anticipate that this work will have direct clinical applications in the context of transplant immunology to improve immunological risk assessment and outcomes after solid organ transplantation.