Defining Clinically Pathogenic HLA-Specific Antibodies - Granular Details in Characteristics in Pre and Early Time Following HLA-Antibody Incompatible Kidney Transplantation

,University Hospitals Of Coventry And Warwickshire Nhs Trust, Coventry Uk ,Adarsh Babu,Natasha Khovanova,Robert Higgins,Warwick Medical School, University Of Warwick, Uk ,School Of Engineering, University Of Warwick, Uk

doi:10.21926/obm.transplant.2103151

, University Hospitals Of Coventry And Warwickshire Nhs Trust, Coventry Uk + Show 5 more

Open Access

https://doi.org/10.21926/obm.transplant.2103151

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Journal: OBM Transplantation	Publication Date: May 11, 2021
License type: cc-by

Affiliation: University of Warwick

Abstract

Antibodies against donor HLA determine access to solid organ transplantation and in many cases the outcome of transplantation, but graft failure is not an inevitable consequence of their presence. Much research has been performed with two main aims – which antibodies represent the highest risk factor prior to transplantation, and second to understand how donor specific HLA antibodies behave after transplantation, with a long-term aim of being able to manipulate their production. HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity. Integral to the understanding of the large datasets generated is sophisticated mathematical analysis using techniques such as decision tree analysis and unsupervised machine learning. This review examines key aspects of this work, performed by us and others.

Highlights

Kidney transplantation is the optimal treatment for patients with end stage kidney disease but immunological barriers, especially HLA antibodies, are important factors limiting timely accessibility to transplantation
HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity
In our cohort of ninety-two highly sensitised patients, we studied for the presence of IgM donor specific antibodies at pre-transplant and at days 7, 14 and 30 post-transplant

Summary

Introduction

Kidney transplantation is the optimal treatment for patients with end stage kidney disease but immunological barriers, especially HLA antibodies, are important factors limiting timely accessibility to transplantation. Assays detecting and defining HLA antibodies have evolved over the last few decades This has allowed us to better understand humoral responses but has posed a major challenge in defining threshold at which we can safely transplant, as we are detecting antibodies at very low levels with increasing sensitivity and specificity. This has redrawn the risk stratification in decision making and increased complexities. Over the last two decades, transplantation across blood group and HLA antibody incompatibilities have been performed successfully in different parts of the world [1,2,3,4,5,6,7] using varied desensitisation therapies [8]. This review summarises current literatures surrounding HLA-specific antibodies and outcome of HLA-incompatible kidney transplantation across the range of immunological risks

Snapshot

MFI Value of HLA-Specific Antibodies

Granular Characterisation of HLA-Specific Antibodies

Class and Subclass Switching

Other Characteristics

Findings

Summary