Number of BAFF-Receptor Molecules on Plasma Cells Prior Kidney Transplantation Identify Patients at Risk of Antibody-Mediated Rejection

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Abstract

Introduction

Despite the increasing interest in antibody-mediated kidney allograft rejection (AbMR), the underlying immunologic mechanisms of this process are not completely understood. B-cell activating factor (BAFF) plays a critical role in the ontogeny of B cells, and the interaction with its receptor, BAFFR, regulate the survival of B cells and plasma cells. Therefore, we aim to analyze the relationship between the differential expression of BAFFR molecules in different cell populations and the appearance of AbMR in kidney transplant recipients.

Introduction

Material and Methods: A cohort of 42 adult kidney transplant recipients, transplanted in Universitary Hospital Marqués de Valdecilla from February 2015 to January 2016 was studied prior performing the surgery. The diagnosis of AbMR was biopsy-proven according to Banff criteria. Protocol biopsies were also performed 12 months after transplantation. B cell subpopulations including naïve, different subsets of immature and transitional B cells, unswitched memory B cells, switched memory B cells and plasma cells were analyzed through multiparametric flow cytometry using CytoFLEX (Beckman Coulter). The expression of BAFFR molecules in the different cell populations was also determined using the same approach.

Results and Discussion

Main patient characteristics are shown in table 1. AbMR was observed in 14.3% of the transplant recipients. 66.7% of them were C4d+ and 100% were g+ptc > 2, according to histologic criteria. No differences between patients suffering AbMR and those patients without any symptom of rejection were found in B cell subpopulation levels. When the expression of BAFFR molecules in plasma cells prior transplantation was measured, a strong correlation with AbMR was observed. Using ROC curves to calculate a cut-off value for the number of BAFFR molecules in plasma cells to discriminate AbMR, 12196 molecules was stablished. Such cut-off reached a sensitivity of 50% and specificity of 96.6% for predicting AbMR. Those patients with higher levels of BAFFR molecules in plasma cells than 12196, were at risk of AbMR [OR 28 (2.1-361.2), p=0.011].

Conclusion

The measurement of BAFFR molecules in plasma cells prior kidney transplantation could be a biomarker of AbMR. Specifically, the detection of higher levels of BAFFR molecules in plasma cells could allow to predict the development of AbMR. However, more and prospective studies should be done to corroborate these data.

Conclusion

Fondo de Investigaciones Sanitarias-ISCIII (PI1100990, PI1400378, PI1601585, and RD16/0009/0027) and IDIVAL.

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