B Cell Markers of Operational Tolerance Can Discriminate Acute Kidney Allograft Rejection From Stable Graft Function.

Heidt, Sebastiaan; Vergunst, Manon; Anholts, J.; Fijter, J. de; Eikmans, Michael; Claas, F.

doi:10.1097/00007890-201407151-03002

Cited by 13 publications

(14 citation statements)

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“…In this study we clearly showed, that this observation is true in tacrolimus treated patients while not in sirolimus patients. Similarly, our group [37] and later Heidt et al [48] have shown that expression levels of B-cell related markers TCL1A , CD79B and MS4A1 were increased in stable and rejection-free patients but decreased at the time of acute rejection, respectively. Similarly, intrarenal B-cell signatures were observed in grafts with better control of acute rejection [49].…”

Section: Discussionsupporting

confidence: 68%

Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial

et al. 2017

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BackgroundThere is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy.MethodsIn this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months.ResultsTAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6–98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up.ConclusionsIn conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full–scale study will be needed to confirm our findings.Trial RegistrationEudraCT Number: 2006-003110-18

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Section: Discussionsupporting

confidence: 68%

Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial

et al. 2017

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“…Previous studies have shown a significant decrease of IgM high CD38 high CD24 high transitional B cells after transplantation . Chung et al .…”

Section: Discussionmentioning

confidence: 94%

Dynamic changes of B-cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection

et al. 2016

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SUMMARYB cells play an important role in the immune responses which affect the outcomes of kidney allografts. Dynamic changes of B-cell compartments in clinical kidney transplantation are still poorly understood. B-cell subsets were prospectively monitored using flow cytometry for 1 year in 98 kidney transplant recipients. Data were correlated with immunosuppression and clinical outcomes. An increase in the total population of B lymphocytes was observed during the first week after transplantation. CD38high CD27 high plasmablasts showed similar kinetics during the first post-transplant year, similar to transitional B cells. In conclusion, sensitized kidney transplant recipients as well as those with either acute or chronic rejection within the first post-transplant year exhibited lower levels of transitional B cells. Therefore, these data further support the hypothesis that transitional B cells have a protective role in kidney transplantation. 2016; 29: 540-548 Transplant International

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“…TCL1A was reported to be overexpressed in TOL in three analyses 17, 21, 28 and to be decreased during acute rejection, stressing the potential of TCL1A as a marker of immune regulation 43, 44 . Similarly, AKR1C3 was also reported to be overexpressed in TOL in three analyses 17, 21, 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in addition to being markers of tolerance, several reports showed that the expression of some of these B cell genes could be used to diagnose patients without acute rejection 43, 44 , suggesting that this score may also be useful to identify immune activation or lack of B cell regulation. Based on sample size and selected nature of the population, tolerance signature may not be universally applicable yet and need further validation on a large cohort of patients.…”

Section: Discussionmentioning

confidence: 99%

A composite score associated with spontaneous operational tolerance in kidney transplant recipients

Danger

Chesneau

Paul

et al. 2017

Kidney International

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New challenges in renal transplantation include using biological information to devise a useful clinical test for discerning high- and low-risk patients for individual therapy and ascertaining the best combination and appropriate dosages of drugs. Based on a 20-gene signature from a microarray meta-analysis performed on 46 operationally tolerant patients and 266 renal transplanted recipients with stable function, we applied the sparse Bolasso methodology to identify a minimal and robust combination of six genes and two demographic parameters associated with operational tolerance. This composite score of operational tolerance discriminated operationally tolerant patients with an area under the curve of 0.97 (95% confidence interval 0.94–1.00). The score was not influenced by immunosuppressive treatment, center of origin, donor type, or post-transplant lymphoproliferative disorder history of the patients. This composite score of operational tolerance was significantly associated with both de novo anti-HLA antibodies and tolerance loss. It was validated by quantitative polymerase chain reaction using independent samples and demonstrated specificity toward a model of tolerance induction. Thus, our score would allow clinicians to improve follow-up of patients, paving the way for individual therapy.

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B Cell Markers of Operational Tolerance Can Discriminate Acute Kidney Allograft Rejection From Stable Graft Function.

Cited by 13 publications

References 0 publications

Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial

Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial

Dynamic changes of B-cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection

A composite score associated with spontaneous operational tolerance in kidney transplant recipients

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