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Published on: August 12, 2017
Belimumab to Aid Pre-Transplant Immunological Risk-Stratification by Uncovering Broader HLA-Specific Memory B-Cell
Dennis A J van den Broek1,2, Gonca E Karahan3,4, Soufian Meziyerh1,2
1Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.
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.
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.
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