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.

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

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 P1715CORRELATION OF DONATED KIDNEY MASS AND GRAFT FUNCTION IN RECIPIENTS OF LIVING DONOR KIDNEY TRANSPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Filipa Silva ◽  
Nicole Pestana ◽  
Catarina Isabel Ribeiro ◽  
Diogo Carneiro ◽  
Mariana Madanelo ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Function ◽  
Significant Risk ◽  
Surrogate Marker ◽  
Kidney Volume ◽  
Post Transplantation ◽  
Donor Kidney ◽  
Live Donor Kidney ◽  
Patients At Risk ◽  
Donor Kidney Transplantation

Abstract Background and Aims Kidney volume has been proven to be a surrogate marker of nephron mass and renal function in living donors. Although many studies correlate the kidney mass with renal donors’ function after donation, few studies have compared the donated kidney mass with estimated glomerular filtration rate (eGFR) in the kidneýs recipients. The purpose of this study is to examine the relationship between donor kidney volume and post-transplantation graft function by using computerized tomography to obtain renal volumes. Method Clinical data off all donor and recipient pairs undergoing live donor kidney transplantation (KT) at our institution between January 2008 and December 2017 (n=195) were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software and correlate to transplant recipient eGFR. Results All metrics of donor kidney volume (DKV): DKV alone, ADK adjusted for weight, body mass index (BMI) or body surface area (BSA), correlated significantly with eGFR (all with p<0,001) at 1 year after KT, with DKV/BSA having the highest correlation (r=0,431). Hence, recipients were divided into terciles according their DKV/BSA (cm3/m2): tercile 1 (DKV/BSA between 49,7-77,5, n=64), tercile 2 (78-95,2, n=63) and tercile 3 (95,4-176, n=63). eGFR differences between groups at each time point were all significant (P<0.05), except for the comparison between T1 and T2 at month 6 (figure 1) Significant risk factors for eGFR<60 ml/min at 1-year were: acute rejection (AR) at 1-year (OR=4.116, P=0.018); calculated PRA>0% (OR=2.075, P=0.039); higher donor age (OR per unit=1.033, P=0.047); and peritoneal dialysis modality (in comparison with preemptive KT: OR=3.232, P=0.013). Higher (T3) DKV/BSA tercile (in comparison with T1: OR=0.306, P=0.004) was protective of this outcome. Patients that experienced AR at 1-year had significantly lower DKV/BSA, particularly those with acute cellular rejection (ACR). The median follow-up was 4,8 years (IQR: 3.2-7.5). The censored graft survival by DKV/BSA terciles at 10 years were 59,3% for group 1, 91.3% for group 2 and 91.1% for group 3 (figure 3). Conclusion Our study demonstrates that transplantation of donor-recipient pairs with lower DKV/BSA ratio were associated with significantly worse graft function and higher incidence of AR. This data suggests that a larger mass of nephrons remaining adjusted to recipient’s weight seems to predict a better long-term eGFR. This method can be useful in order to identify patients at risk for a low eGFR after KT and, in cases of multiple potential donors, optimize donor selection.

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 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 De novo ulcerative colitis after kidney transplantation treated with infliximab

2021 ◽  
Author(s):  
Rikako Oki ◽  
Sumi Hidaka ◽  
Akiko Sasaki ◽  
Shinichi Teshima ◽  
Yasuhiro Mochida ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Kidney Transplantation ◽  
De Novo ◽  
Graft Function ◽  
Bloody Diarrhea ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Common Causes ◽  
Factor Α ◽  
End Stage

AbstractDiarrhea is a common complication in kidney transplant recipients. Common causes of diarrhea include infection, side effect from medication, rejection, and malignancy. A less common but important cause of diarrhea is de novo inflammatory bowel disease (IBD). This is unexpected, as these patients are already immunosuppressed. Herein, we present the case of a 45-year-old man with end-stage kidney disease because of focal segmental glomerulosclerosis who underwent preemptive kidney transplantation, with his mother as donor. His immunosuppressive regimen included methylprednisolone, mycophenolate mofetil, and tacrolimus. He had no episodes of graft dysfunction, rejection, or infectious events. Two and a half years post-transplantation, he developed bloody diarrhea. After excluding infections, colonoscopy was performed and revealed edematous mucosa and erythema with pigmentation, which are typical findings in ulcerative colitis. Despite therapy with 5-aminosalicylate and granulocyte monocyte apheresis, he presented with massive bloody diarrhea. We initiated infliximab, an anti-tumor necrosis factor-α (TNF-α) agent. He responded very well and achieved remission within 6 months after initiation of infliximab, while administration of the other immunosuppressants was maintained. His course was uneventful and no complications developed. Management of immunosuppressants for de novo IBD after organ transplantation is complicated, because treatment of IBD, graft function protection, and prevention of infection must be considered. Therefore, cooperation between transplantation physicians and gastroenterologists is essential during therapy.

P1740KINETICS OF B-CELL SUBSETS RECONSTITUTION FOLLOWING RITUXIMAB TREATMENT IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yamei Li ◽  
Yunying Shi ◽  
Tao Lin ◽  
Xianding Wang ◽  
Lin Yan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Kidney Transplant ◽  
Cell Population ◽  
Immune Cell ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Antibody Mediated Rejection ◽  
B Cell Subsets

Abstract Background and Aims With the application of B-cell-depleting agent rituximab, plasmapheresis and powerful immunosuppression, ABO-incompatible kidney transplant recipients (ABOi-KT) have successfully overcome the ABO antibody barrier. As an important immune cell population, B cells are not only involved in antibody-mediated rejection, but also have been reported to have different immunoregulatory effects due to the existence of distinct B cell subsets. Therefore, comprehensively understanding the reconstitution of B-cell subsets in ABOi-KTRs is crucial to know the immune status that may be related to the subsequent complications. Method Fresh whole blood were collected from 22 ABOi-KTRs and 22 ABO-compatible recipients (ABOc-KTRs) at 0, 1week, 2 weeks ,1month, 3months, and 6 months post-transplantation between October 2018 and May 2019. In addition, pre-desensitization samples were also collected from ABOi-KTRs. B cell subsets including total, naïve, memory, plasma, plasma blast and regulatory B cells were determined by flow cytometry. Results The percentages of B cells in ABOi group remained extremely low and significantly lower than ABOc group through the first 6 months after rituximab treatment (Fig. A). Similar trends were observed in total memory and switched memory B cells whose frequencies increased within first 2 weeks, then decreased thereafter. Meanwhile, the significant differences between ABOi and ABOc groups disappeared at 6 months (Fig. B-D). In addition, plasma and plasma blast B cells increased 2 weeks after transplantation and were significantly higher in ABOi group compared to ABOc group (Fig. E, G), while Naïve B cells started to elevate 1 month after transplantation in ABOi-KTRs and significantly higher proportions were found in ABOc group through the entire 6 months (Fig. F). No obvious difference was observed between ABOi and ABOc groups regarding unswitched memory and regulatory B cell percentages (Fig. C, H). Conclusion Our preliminary results indicated that B-cell depletion therapy applied in ABOi-KTRs not only significantly reduced the number of B cells, but also changed the composition of B cell subsets in the remaining B cell population. Whether such alteration would be clinical significance requires further follow-up.

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.

scholarly journals The EKiTE network (epidemiology in kidney transplantation - a European validated database): an initiative epidemiological and translational European collaborative research

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
M. Lorent ◽  
◽  
Y. Foucher ◽  
K. Kerleau ◽  
S. Brouard ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Clinical Epidemiology ◽  
Main Body ◽  
Large Set ◽  
Kidney Transplant Recipients ◽  
Clinical Practices ◽  
Post Transplantation ◽  
Wide Range ◽  
Epidemiology Studies ◽  
Transplantation Outcomes

Abstract Background Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies. Main body Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses. Conclusion EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.

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