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.

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 Circulating exosomal lncRNAs in patients with chronic coronary syndromes

2021 ◽  
Author(s):  
Meili Zheng ◽  
Ruijuan Han ◽  
Wen Yuan ◽  
Hongjie Chi ◽  
Yeping Zhang ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Case Control Study ◽  
Diagnostic Value ◽  
Pcr Analysis ◽  
Roc Curve Analysis ◽  
Coronary Syndrome ◽  
Qrt Pcr ◽  
Coronary Syndromes ◽  
European Society Of Cardiology ◽  
Control Study

IntroductionThe concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear.Material and methodsA case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients.ResultsA total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028).ConclusionsExosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

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

Dynamics of soluble syndecan-1 in maternal serum during and after pregnancies complicated by preeclampsia: a nested case control study

2019 ◽  
Vol 58 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Lorenz Kuessel ◽  
Heinrich Husslein ◽  
Eliana Montanari ◽  
Michael Kundi ◽  
Gottfried Himmler ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Predictive Power ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Serum Levels ◽  
Maternal Serum ◽  
Nested Case Control ◽  
Single Time Point ◽  
Control Study

Abstract Background We investigated the dynamics and the predictive value of soluble syndecan-1 (Sdc-1), a biomarker of endothelial dysfunction, in uneventful pregnancies and pregnancies complicated by preeclampsia (PE). Methods Serum levels of Sdc-1 were measured at sequential time points during and after uneventful pregnancies (control, n = 95) and pregnancies developing PE (PE_long, n = 12). Levels were further measured in women with symptomatic PE (PE_state, n = 46) at a single time point. Results Sdc-1 levels increased consistently throughout pregnancy. In the PE_long group Sdc-1 levels were lower at all visits throughout pregnancy, and reached significance in weeks 18–22 (p = 0.019), 23–27 (p = 0.009), 28–32 (p = 0.006) and 33–36 (p = 0.008). After delivery, Sdc-1 levels dropped sharply in all pregnancies but were significantly elevated in the PE_long group. The predictive power of Sdc-1 was evaluated analyzing receiver operating characteristic (ROC) curves. A significant power was reached at weeks 14–17 (area under the curve [AUC] 0.65, p = 0.025), 23–27 (AUC 0.73, p = 0.004) and 33–36 (AUC 0.75, p = 0.013). Conclusions In summary, Sdc-1 levels were lower in women developing PE compared to uneventful pregnancies and Sdc-1 might be useful to predict PE. After delivery, Sdc-1 levels remained higher in women with PE. Additional studies investigating the link between glycocalyx degradation, Sdc-1 levels and placental and endothelial dysfunction in pregnancies affected by PE are warranted.

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 Comparison of the Morphological and Biomechanical Characteristics of Keratoconus, Forme Fruste Keratoconus, and Normal Corneas

2020 ◽  
Author(s):  
Li-Li Guo ◽  
Lei Tian ◽  
Kai Cao ◽  
Yu-Xin Li ◽  
Na Li ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Operating Characteristic ◽  
Case Control Study ◽  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Corneal Surface ◽  
Biomechanical Parameters ◽  
Low Efficiency ◽  
Control Study ◽  
Forme Fruste Keratoconus

Abstract Background: To explore the feasibility of corneal morphological and biomechanical parameters for keratoconus and forme fruste keratoconus diagnosis.Methods: This case-control study included a total of 517 eyes from 408 keratoconus patients (KC group), 83 eyes from 83 forme fruste keratoconus patients (FFKC group), and 158 eyes from 158 patients with normal corneas (NL group). All subjects underwent routine ophthalmology examinations. Pentacam and Corneal Visualization Scheimpflug Technology were used to obtain corneal morphological and biomechanical parameters. Differences between the groups were compared using receiver operating characteristic (ROC) curve analysis.Results: Comparison of the NL group with the KC and FFKC groups (P<0.05), and the NL and KC groups alone (P<0.017), revealed statistically significant differences in corneal morphological and biomechanical parameters, except time from the start until the highest concavity (HCT), deflection length of the first applanation (A1 DfL), and deflection length of the second applanation (A2 DfL). Comparison of the NL and FFKC groups revealed 12 significantly different parameters (P<0.017). ROC analysis showed that all corneal morphological parameters and most biomechanical parameters distinguished KC from NL, with an area under the curve (AUC) greater than 0.80, of which Belin-Ambrósio enhanced ectasia total deviation index (BAD-D) and tomographic and biomechanical index (TBI) were most efficient. Except for central astigmatism from the anterior corneal surface (AstigF), the AUC that distinguished FFKC from NL was 0.862. Other parameters distinguished FFKC from NL with low efficiency. Conclusion: All corneal morphological and most biomechanical parameters are different in KC versus NL, but only a few parameters are different in FFKC versus NL. BAD-D and TBI have the highest efficiency, sensitivity, and specificity for distinguishing KC from NL. The parameters had a low ability to distinguish FFKC from NL. The application of biomechanical instruments to diagnose early keratoconus needs further study.

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