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

Irure‐Ventura, Juan; Segundo, David San; Rodrigo, Emilio; Merino, David; Vega, Lara Belmar; Ruiz, J.C.; Valero, Rosalía; Benito, Adalberto; López‐Hoyos, Marcos

doi:10.3390/ijms21030779

Cited by 9 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They observed both cohorts over a period of 6 months. In the work of Irure-Ventura et al, increased BAFF values before transplantation were associated with an increased occurrence of antibody-mediated rejection in the first 12 months [21]. In contrast to these examinations and the results of our cohort, the patients with ABMR in the work of Slavcec stood out due to the low BAFF level.…”

Section: Discussioncontrasting

confidence: 82%

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

et al. 2021

View full text Add to dashboard Cite

The 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.

show abstract

Section: Discussioncontrasting

confidence: 82%

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll Histopaque 1077 (Sigma Aldrich, St. Louis, MI, USA) gradient centrifugation. In brief, PBMCs were freshly stained and processed following standard procedures [ 12 , 13 ]. The following monoclonal antibodies were used to identify the pT FH and the different T lymphocyte subsets: CD45-Krome orange (KrO) clone J33, CD3-pacific blue (PB) clone UCHT1, CD4-phycoerythrin-cyanine 5.5 (PC5.5) clone 13B8.2, CD45RO-ECD clone UCHL1, (Beckman Coulter, Brea, CA, USA), CXCR3-FITC clone G025H7, CCR6 (CD196) phycoerythrin-cyanine 7 (PE Cy7) clone G034E3, and CXCR5-PE clone J252D4 (BioLegend, San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Immune Assessment of BNT162b2 m-RNA-Spike Based Vaccine Response in Adults

et al. 2021

Self Cite

View full text Add to dashboard Cite

Vaccine efficacy is based on clinical data. Currently, the assessment of immune response after SARS-CoV-2 vaccination is scarce. A total of 52 healthcare workers were immunized with the same lot of BNT162b2 vaccine. The immunological response against the vaccine was tested using a T-specific assay based on the expression of CD25 and CD134 after stimulation with anti-N, -S, and -M specific peptides of SARS-CoV-2. Moreover, IgG anti-S2 and -RBD antibodies were detected using ELISA. Furthermore, the cell subsets involved in the response to the vaccine were measured in peripheral blood by flow cytometry. Humoral-specific responses against the vaccine were detected in 94% and 100% after the first and second doses, respectively. Therefore, anti-S T-specific responses were observed in 57% and 90% of the subjects after the first and second doses of the vaccine, respectively. Thirty days after the second dose, significant increases in T helper 1 memory cells (p < 0.001), peripheral memory T follicular helper (pTFH) cells (p < 0.032), and switched memory (p = 0.005) were observed. This study describes the specific humoral and cellular immune responses after vaccination with the new mRNA-based BNT162b2 vaccine. A mobilization of TFH into the circulation occurs, reflecting a specific activation of the immune system.

show abstract

“…Elevations in plasma BAFF levels have been implicated in several autoimmune disease processes leading to the development of a clinically approved -BAFF mAb, belimumab (45)(46)(47)(48). Recent studies in allograft transplant recipients demonstrate that high BAFF levels prior to transplant are associated with antibodymediated rejection and elevated levels following -CD20 therapy may also contribute to the failure to induce humoral tolerance to the graft (49)(50)(51). Using both adult and pediatric HA patient samples and HA mouse models, here we investigate the hypothesis that BAFF may play a role in the generation and sustenance of -FVIII antibodies, especially in the context of -CD20 therapy, which may influence therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

B cell–activating factor modulates the factor VIII immune response in hemophilia A

Doshi¹,

Rana²,

Castaman³

et al. 2021

Journal of Clinical Investigation

View full text Add to dashboard Cite

Inhibitors to factor VIII (FVIII) remain the most challenging complication of FVIII protein replacement therapy in hemophilia A (HA). Understanding the mechanisms that guide FVIII-specific B cell development could help identify therapeutic targets. The B cell activating factor (BAFF) cytokine family is a key regulator of B cell differentiation in normal homeostasis and immune disorders. Thus, we used patient samples and mouse models to investigate the potential role of BAFF in modulating FVIII inhibitors. BAFF levels were elevated in pediatric and adult HA inhibitor patients and decreased to levels similar to non-inhibitor controls after successful immune tolerance induction (ITI). Moreover, elevations in BAFF levels were seen in patients who failed to achieve FVIII tolerance with anti-CD20 mediated B-cell depletion. In naïve HA mice, prophylactic anti-BAFF therapy prior to FVIII immunization prevented inhibitors and this tolerance was maintained despite FVIII exposure after immune reconstitution. In preimmunized HA mice, combination therapy with anti-CD20 and anti-BAFF antibodies dramatically reduced FVIII inhibitors via inhibition of FVIII-specific plasma cells. Our data suggest that BAFF may regulate the generation and maintenance of FVIII inhibitors and/or anti-FVIII B cells. Finally, anti-CD20/anti-BAFF combination therapy may be clinically useful for ITI.

show abstract

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

Cited by 9 publications

References 51 publications

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

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

Immune Assessment of BNT162b2 m-RNA-Spike Based Vaccine Response in Adults

B cell–activating factor modulates the factor VIII immune response in hemophilia A

Contact Info

Product

Resources

About