Belimumab to Aid Pre-Transplant Immunological Risk-Stratification by Uncovering Broader HLA-Specific Memory B-Cell Profiles

Abstract

Highly sensitised kidney transplant candidates face substantial barriers to transplantation due to limited donor compatibility. Delisting unacceptable antigens with detectable HLA-specific antibodies can improve transplant access. It is, however, challenging to determine which specificities are safe to delist. Assessment of circulating HLA-specific memory B-cells may support risk stratification. However, current methodologies are limited by the predominant localisation of memory B-cells in secondary lymphoid organs and thus by potential false negativity. BAFF inhibitors, such as belimumab, mobilise memory B-cells into the circulation, which could reduce false-negative evaluations and improve pretransplant risk stratification. We administered off-label treatment with 200 mg of subcutaneous belimumab weekly for 4 weeks to seven highly sensitised patients with limited allocation probability. The clinical aim was to safely increase allocation probability by selectively delisting unacceptable HLA-specificities without detectable B-cell memory. HLA-specific memory B-cell profiles were assessed before and after treatment, revealing significantly broader HLA-specific memory B-cell profiles after belimumab in addition to a significant increase of HLA-antibody MFI in the eluate of stimulated memory B-cells. This strategy may pave the way for a new paradigm in pretransplant immunological risk-stratification, allowing improved assessment of HLA-specific memory B-cell profiles, which could potentially limit the risk of memory responses.