Dataset Information

A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients.

ABSTRACT:

Background

Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies.

Methods

This prospective pilot randomized French multicenter study aimed to compare anti-T-lymphocyte Ig (ATLG) (n = 32) and basiliximab (n = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included.

Results

Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%-37.1%) and 18.8% (95% CI, 8.9%-37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%-34.8%) and 28.2% (95% CI, 14.2%-51.2%) of patients who received basiliximab, respectively at 6 (P = 0.66) and 12 (P = 0.62) months post-transplantation. One T cell-mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a de novo donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups.

Conclusion

This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution.

SUBMITTER: Kamar N

PROVIDER: S-EPMC7403559 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients.

Kamar Nassim N Lepage Benoit B Couzi Lionel L Albano Laetitia L Durrbach Antoine A Pernin Vincent V Esposito Laure L Hebral Anne Laure AL Darres Amandine A Lequintrec Moglie M Cassuto Elisabeth E Merville Pierre P Congy Nicolas N Del Bello Arnaud A

Kidney international reports 20200602 8

<h4>Background</h4>Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies.<h4>Methods</h4>This prospective pilot randomized French multicenter study aimed to compare anti-T-lymphocyte Ig (ATLG) (<i>n</i> = 32) and basiliximab (<i>n</i> = 27) in highly sensitized kidney-trans ...[more]

PMID: 32775820

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Project description:BackgroundPre-sensitized kidney transplant recipients have a higher risk for rejection following kidney transplantation and therefore receive lymphodepletional induction therapy with anti-human T-lymphocyte globulin (ATLG) whereas non-sensitized patients are induced in many centers with basiliximab. The time course of lymphocyte reconstitution with regard to the overall and donor-reactive T-cell receptor (TCR) specificity remains elusive.Methods/designFive kidney transplant recipients receiving a 1.5-mg/kg ATLG induction therapy over 7 days and five patients with 2 × 20 mg basiliximab induction therapy were longitudinally monitored. Peripheral mononuclear cells were sampled pre-transplant and within 1, 3, and 12 months after transplantation, and their overall and donor-reactive TCRs were determined by next-generation sequencing of the TCR beta CDR3 region. Overall TCR repertoire diversity, turnover, and donor specificity were assessed at all timepoints.ResultsWe observed an increase in the donor-reactive TCR repertoire after transplantation in patients, independent of lymphocyte counts or induction therapy. Donor-reactive CD4 T-cell frequency in the ATLG group increased from 1.14% + -0.63 to 2.03% + -1.09 and from 0.93% + -0.63 to 1.82% + -1.17 in the basiliximab group in the first month. Diversity measurements of the entire T-cell repertoire and repertoire turnover showed no statistical difference between the two induction therapies. The difference in mean clonality between groups was 0.03 and 0.07 pre-transplant in the CD4 and CD8 fractions, respectively, and was not different over time (CD4: F(1.45, 11.6) = 0.64 p = 0.496; CD8: F(3, 24) = 0.60 p = 0.620). The mean difference in R20, a metric for immune dominance, between groups was -0.006 in CD4 and 0.001 in CD8 T-cells and not statistically different between the groups and subsequent timepoints (CD4: F(3, 24) = 0.85 p = 0.479; CD8: F(1.19, 9.52) = 0.79 p = 0.418).ConclusionReduced-dose ATLG induction therapy led to an initial lymphodepletion followed by an increase in the percentage of donor-reactive T-cells after transplantation similar to basiliximab induction therapy. Furthermore, reduced-dose ATLG did not change the overall TCR repertoire in terms of a narrowed or skewed TCR repertoire after immune reconstitution, comparable to non-depletional induction therapy.

Project description:BackgroundKidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy.Methods and findingsSingle-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy.ConclusionsMeasuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates.

Project description:Background and Objectives: The aim of our study was to categorize very highly sensitized kidney transplant recipients with pre-transplant panel reactive antibody (PRA) ≥ 98% using an unsupervised machine learning approach as clinical outcomes for this population are inferior, despite receiving increased allocation priority. Identifying subgroups with higher risks for inferior outcomes is essential to guide individualized management strategies for these vulnerable recipients. Materials and Methods: To achieve this, we analyzed the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database from 2010 to 2019 and performed consensus cluster analysis based on the recipient-, donor-, and transplant-related characteristics in 7458 kidney transplant patients with pre-transplant PRA ≥ 98%. The key characteristics of each cluster were identified by calculating the standardized mean difference. The post-transplant outcomes were compared between the assigned clusters. Results: We identified two distinct clusters and compared the post-transplant outcomes among the assigned clusters of very highly sensitized kidney transplant patients. Cluster 1 patients were younger (median age 45 years), male predominant, and more likely to have previously undergone a kidney transplant, but had less diabetic kidney disease. Cluster 2 recipients were older (median 54 years), female predominant, and more likely to be undergoing a first-time transplant. While patient survival was comparable between the two clusters, cluster 1 had lower death-censored graft survival and higher acute rejection compared to cluster 2. Conclusions: The unsupervised machine learning approach categorized very highly sensitized kidney transplant patients into two clinically distinct clusters with differing post-transplant outcomes. A better understanding of these clinically distinct subgroups may assist the transplant community in developing individualized care strategies and improving the outcomes for very highly sensitized kidney transplant patients.

Dataset Information

A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients.

Background

Methods

Results

Conclusion

Publications

A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients.

Similar Datasets

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