B-cell activating factor, a predictor of antibody mediated rejection in kidney transplantation recipients

Nephrology ◽  
2018 ◽  
Vol 23 (2) ◽  
pp. 169-174 ◽  
Author(s):  
Wannarat Pongpirul ◽  
Wiwat Chancharoenthana ◽  
Krit Pongpirul ◽  
Asada Leelahavanichkul ◽  
Wipawee Kittikowit ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Antibody Mediated Rejection ◽  
B Cell Activating Factor

scholarly journals B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation

2021 ◽  
Author(s):  
Antonia Margarete Schuster ◽  
N. Miesgang ◽  
L. Steines ◽  
C. Bach ◽  
B. Banas ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Graft Function ◽  
Risk Profile ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Antibody Mediated Rejection ◽  
B Cell Activating Factor ◽  
Medium Risk ◽  
Patients At Risk

AbstractThe B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

scholarly journals B Cell Activating Factor, Renal Allograft Antibody-Mediated Rejection, and Long-Term Outcome

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Haiyan Xu ◽  
Xiaozhou He ◽  
Renfang Xu
Keyword(s):  
B Cell ◽  
Renal Allograft ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Direct Proof ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Antibody Mediated Rejection ◽  
B Cell Activating Factor

Antibody-mediated rejection (ABMR) of renal allograft lacks typical phenotypes and clinical manifestations, always resulting in delayed diagnosis and treatment. It has been considered to be an elemental factor influencing the improvement of the long-term outcome of renal allograft. The B cell activating factor (BAFF) signal plays a fundamental function in the process of antibody-mediated immune response. Data from recipients and the nonhuman primate ABMR model suggest that the BAFF signal participates in the ABMR of renal allograft, while there are objections. The challenges in the diagnosis of ABMR, different study population, and details of research may explain the discrepancy. Large quantities of dynamic, credible data of BAFF ligands and their association with renal allograft pathological characteristics would constitute a direct proof of the role of BAFF in the progression of renal allograft ABMR.

B-cell activating factor BAFF reflects patients' immunological risk profile after kidney transplantation

2017 ◽  
Vol 45 ◽  
pp. 35-41 ◽  
Author(s):  
A. Schuster ◽  
B. Jung ◽  
J. Hofbauer ◽  
L. Kühne ◽  
D. Zecher ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Risk Profile ◽  
B Cell Activating Factor

B-Cell Activating Factor BAFF Reflects Patients’ immunological Risk Profile after Kidney Transplantation

2018 ◽  
Vol 102 ◽  
pp. S715
Author(s):  
Antonia Schuster ◽  
Bettina Jung ◽  
Louisa Kühne ◽  
Bernhard Banas ◽  
Tobias Bergler
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Risk Profile ◽  
B Cell Activating Factor

scholarly journals Tocilizumab and Desensitization in Kidney Transplant Candidates: Personal Experience and Literature Review

2021 ◽  
Vol 10 (19) ◽  
pp. 4359
Author(s):  
Jules Weinhard ◽  
Johan Noble ◽  
Thomas Jouve ◽  
Paolo Malvezzi ◽  
Lionel Rostaing
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Cell Maturation ◽  
Post Transplantation ◽  
No Donor ◽  
Antibody Mediated Rejection ◽  
Term Efficacy ◽  
B Cell Maturation ◽  
Mesh Terms

Desensitization (DES) allows kidney transplantation for highly HLA-sensitized subjects. Due to the central role of IL-6 in the immunological response, tocilizumab may improve DES efficacy. Thus, we conducted a PubMed systematic review using the MeSH terms tocilizumab, interleukin-6, kidney transplantation, and desensitization. Tocilizumab (TCZ) was first studied for DES as the second-line treatment after failure of a standard DES protocol (SP) (apheresis, rituximab +/- IVIg). Although TCZ (as a monotherapy) attenuated anti-HLA antibody rates, it did not permit transplantation. However, lymphocyte immuno-phenotyping has shown that TCZ hinders B-cell maturation and thus could improve the long-term efficacy of DES by limiting anti-HLA rebound and so avoid antibody-mediated rejection. This hypothesis is supported by a recent study where clazakizumab, a monoclonal antibody directed against IL-6, was continued after kidney transplantation in association with an SP. Nine out of ten patients were then eligible for transplantation, and there were no donor-specific antibodies at 6 months post-transplantation. In association with an SP, tocilizumab does not seem to significantly improve kidney-allograft access (short-term efficacy) vs. a SP only. However, it could improve the long-term prognosis of HLA-incompatible transplantation by hindering B-cell maturation and, thereby, avoiding donor-specific antibody rebounds post-transplantation.

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

2020 ◽  
Vol 21 (3) ◽  
pp. 779 ◽  
Author(s):  
Juan Irure-Ventura ◽  
David San Segundo ◽  
Emilio Rodrigo ◽  
David Merino ◽  
Lara Belmar-Vega ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Graft Loss ◽  
Cell Subset ◽  
Predictive Biomarkers ◽  
Antibody Mediated Rejection ◽  
Non Invasive ◽  
Transplant Patients ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

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.

scholarly journals Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney Transplantation

2020 ◽  
Vol 31 (10) ◽  
pp. 2457-2474
Author(s):  
Kevin Louis ◽  
Camila Macedo ◽  
Elodie Bailly ◽  
Louis Lau ◽  
Bala Ramaswami ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cells ◽  
B Cell ◽  
Rna Sequencing ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Follicular Helper ◽  
Allograft Loss ◽  
Activated B Cells

BackgroundAlthough antibody-mediated rejection (ABMR) has been long recognized as a leading cause of allograft failure after kidney transplantation, the cellular and molecular processes underlying the induction of deleterious donor-specific antibody (DSA) responses remain poorly understood.MethodsUsing high-dimensional flow cytometry, in vitro assays, and RNA sequencing, we concomitantly investigated the role of T follicular helper (TFH) cells and B cells during ABMR in 105 kidney transplant recipients.ResultsThere were 54 patients without DSAs; of those with DSAs, ABMR emerged in 20 patients, but not in 31 patients. We identified proliferating populations of circulating TFH cells and activated B cells emerging in blood of patients undergoing ABMR. Although these circulating TFH cells comprised heterogeneous phenotypes, they were dominated by activated (ICOS+PD-1+) and early memory precursor (CCR7+CD127+) subsets, and were enriched for the transcription factors IRF4 and c-Maf. These circulating TFH cells produced large amounts of IL-21 upon stimulation with donor antigen and induced B cells to differentiate into antibody-secreting cells that produced DSAs. Combined analysis of the matched circulating TFH cell and activated B cell RNA-sequencing profiles identified highly coordinated transcriptional programs in circulating TFH cells and B cells among patients with ABMR, which markedly differed from those of patients who did not develop DSAs or ABMR. The timing of expansion of the distinctive circulating TFH cells and activated B cells paralleled emergence of DSAs in blood, and their magnitude was predictive of IgG3 DSA generation, more severe allograft injury, and higher rate of allograft loss.ConclusionsPatients undergoing ABMR may benefit from monitoring and therapeutic targeting of TFH cell–B cell interactions.

scholarly journals Elevated Circulating IL-10 Producing Breg, but Not Regulatory B Cell Levels, Restrain Antibody-Mediated Rejection After Kidney Transplantation

2021 ◽  
Vol 11 ◽  
Author(s):  
Yongsheng Luo ◽  
Feifei Luo ◽  
Kuanxin Zhang ◽  
Shilei Wang ◽  
Haojie Zhang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
B Cell ◽  
Operating Characteristic ◽  
Roc Curve Analysis ◽  
Regulatory B Cell ◽  
Antibody Mediated Rejection ◽  
Healthy Donors ◽  
Post Operation ◽  
Nested Case Control ◽  
Control Study

BackgroundAntibody-mediated rejection (AMR) occupies a major position for chronic rejection after kidney transplantation. Regulatory B cell (Breg) has been reported to have an inhibitory immune function, which contributes to the resistance for AMR.MethodsA nested case–control study for nine healthy donors, 25 stable (ST) patients, and 18 AMR patients was performed to determine the type of Breg in maintaining immune tolerance and preventing AMR.ResultsCompared to the ST group, circulating interleukin (IL)-10+ Bregs, but not Bregs, significantly decreased. The receiver operating characteristic (ROC) curve analysis revealed that rather than the circulating Bregs, decreased circulating IL-10+ Breg levels were positively associated with AMR. However, kidney B cell and IL-10 infiltration was significantly increased in the AMR group with high expression of C-X-C motif chemokine 13 (CXCL13). In addition, circulating IL-10+ Bregs, rather than Bregs, remained higher than those at pre-operation, during the 90-day post-operation in immune homeostasis.ConclusionThe circulating IL-10+ Breg levels are more appropriate measures for assessing the resistance of AMR after kidney transplantation.

P1617RENAL TRANSPLANT PATIENTS HARBOR NEUTROPHILS SECRETING B-CELL ACTIVATING FACTOR (BAFF) WHICH CAN BE SUPPRESSED BY MTOR INHIBITORS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hannah Steinberg ◽  
Sebastian Dolff ◽  
Andreas Kribben ◽  
Xin Ma ◽  
Oliver Witzke ◽  
...  
Keyword(s):  
Renal Transplant ◽  
B Cell ◽  
Mtor Inhibitors ◽  
Colony Stimulating Factor ◽  
Antibody Mediated Rejection ◽  
Transplant Patients ◽  
B Cell Activating Factor ◽  
Increased Risk ◽  
Renal Transplant Patients ◽  
Stimulating Factor

Abstract Background and Aims B cell activating factor (BAFF) is a cytokine which drives B cell survival and maturation. Several studies have shown that elevated BAFF levels in renal transplant patients are associated with increased risk for the development of donor specific antibodies and antibody mediated rejection. It was the aim of this study to investigate neutrophils as cellular source of BAFF in renal transplant patients. Method Neutrophils (NT) were freshly isolated from whole blood of healthy controls (HC) and renal transplant patients (RTX). After isolation, purity of neutrophils was usually above 98%. Neutrophils were stimulated with LPS or TNFα in presence of Granulocyte-colony stimulating factor (GCSF) or Granulocyte macrophage colony-stimulating factor (GMCSF). In selected conditions, FK506 or rapamycin was added. Supernatants were harvested after 20 hours of culture and BAFF levels were determined by ELISA. Results GCSF/TNFα and GCSF/LPS were the most potent stimuli leading to BAFF secretion of NT in HC (403 ±64 pg/ml and 421 ±69 pg/ml). NT derived RTX showed similar capacity to secrete BAFF as compared to HC (GCSF/TNFα: 515 ±31 pg/ml and GCSF/LPS: 539.4 ±36 pg/ml). Treatment of cultures with rapamycin reduced BAFF levels (515 ±100 pg/ml vs. 348 ±27 pg/ml, p<0.001). Treatment with FK506 was less efficacious (515 ±31 pg/ml vs. 465 ±31 pg/ml, p=0.01). Conclusion NT may enhance of B cell maturation and survival via BAFF. BAFF-secretion by NT can be suppressed with mTOR inhibitors. In renal transplantation, NT might promote formation of allo-antibodies and drive antibody mediated rejection.

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