High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection.

Juan Irure-Ventura,Lara Belmar-Vega,Marcos López-Hoyos,Rosalía Valero,David Merino,Adalberto Benito,David San Segundo,Juan Carlos Ruiz San Millán,Emilio Rodrigo

doi:10.3390/ijms21030779

Abstract

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the effect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who suffered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR.

Highlights

The importance of B cells in kidney transplantation, especially in the case of antibody-mediated rejection (AbMR) and transplantation tolerance, has been highlighted in recent studies [1,2,3]
Unlike the results showed by different groups where no differences were found in BAFF levels between kidney transplant recipients and controls [31] indicating that this molecule is not a prognostic marker for allograft dysfunction, or that no correlation exists between BAFF and the production of donor-specific antibodies (DSA) before and after transplantation [32], in the present study we observed that patients with AbMR
Taking all of this into account and considering the results that we have obtained, we suggest that pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of antibody-mediated rejection, independently of classical variables

Summary

Introduction

The importance of B cells in kidney transplantation, especially in the case of antibody-mediated rejection (AbMR) and transplantation tolerance, has been highlighted in recent studies [1,2,3]. It is well known the crucial role of B cells in humoral immunity, but they contribute in other important processes, such as co-stimulation, antigen presentation, and cytokine secretion, all of them mechanisms that modulate the function of T cells [4]. The B cell homeostasis is modulated by different soluble factors, mainly the B-cell activating factor (BAFF, known as TNFSF13B or the B lymphocyte stimulator, BLyS) and proliferation-inducing ligand (APRIL). TACI is expressed in B cells upon activation, whereas BCMA is found in germinal center B cells and in terminally differentiated B cells [11]

Methods

Results

Conclusion