Biomarkers to assess donor-reactive T-cell responses in kidney transplant patients

Crespo, Elena; Bestard, Oriol

doi:10.1016/j.clinbiochem.2015.08.010

Cited by 13 publications

(8 citation statements)

References 109 publications

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“…In fact, cross-reactive T-cell memory through molecular mimicry (so-called heterogeneous immunity) has been shown to lead to the development of alloresponses. 28 Contrary to previous observations, we did not find evidence of increased frequency of regulatory T cells 29 or gd T cells 30 among the LTA recipients compared with KTA patients. Strikingly, the frequency of regulatory T cells was low among the SLK patients.…”

Section: Discussioncontrasting

confidence: 99%

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year

Taner

Gustafson

Hansen

et al. 2018

Kidney International

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Section: Discussioncontrasting

confidence: 99%

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year

Taner

Gustafson

Hansen

et al. 2018

Kidney International

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“…We did not find any association between a positive pre-transplant d-sp ELISPOT and worse allograft function progression after transplantation. Nonetheless, while some studies have showed such correlation, particularly among patients not receiving T-cell induction therapy [ 14 , 20 ], some other groups have not been able to find such association before transplantation [ 8 , 13 , 16 , 34 , 35 ] but have conversely found a consistent relationship between worse kidney allograft function progression and the d-sp ELISPOT when assessed after transplantation suggesting a much close illustration of the on-going anti-donor T-cell alloimmune response of transplant patients.…”

Section: Discussionmentioning

confidence: 99%

“…The notion that alloreactive memory T cells (Tmem) are crucial mediators of allograft rejection led to the development of the cytokine enzyme-linked immunospot (ELISPOT) assay which is able to quantify circulating alloreactive Tmem at the single cell level [ 12 , 13 ]. Initial studies have shown that pre-transplantation d-sp ELISPOT correlates with biopsy-proven acute rejection (BPAR) after kidney transplantation [ 14 , 15 ] and could be used to tailor immunosuppression [ 16 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation

et al. 2018

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Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT) and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after kidney transplantation. Adding IL15 to the PRT assay (PRT+IL15) may uncover the presence of pathogenic alloreactive CD28-Tmem. Face-to-face comparisons of these assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT assays (±IL15, against six B-cell lines) in 168 consecutive kidney transplant recipients and evaluated the multivariable-adjusted associations with biopsy-proven acute rejection (BPAR), de novo donor-specific antibodies (DSA), and eGFR decline over a 48-month follow-up period. D-sp ELISPOT was positive in 81 (48%) subjects, while 71 (42%) and 81 (48%) subjects displayed positive PRT and PRT+IL15, respectively. Their median [interquartile range] numerical test result was 23 [6–65], 18 [8–37], and 26 [10–45] spots/3x105 PBMCs, respectively. The number of PRT spots were weakly correlated with those of d-sp ELISPOT, but highly correlated with PRT+IL15 (rho = 0.96, P<0.001). d-sp ELISPOT, but not PRT (±IL15) was independently associated with BPAR (adjusted Odds Ratio of BPAR associated with d-sp ELISPOT positivity: 4.20 [95%CI: 1.06 to 21.73; P = 0.041]). Unlike d-sp ELISPOT, median PRT and PRT+IL15 were independently associated with higher Δ3-48month eGFR decline post-transplantation (for both assays, about -3mL/min/1.73m2 per one standard deviation unit increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays identifies kidney transplant candidates at high risk of BPAR and worse kidney allograft progression.

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“…The risk of AR is currently estimated with pretransplant assessment of DSAs, and HLA mismatch; however, alloreactive memory T-cell responses are not measured with these assays. The presence of alloreactive T cells pretransplantation can lead to rapid recognition of alloantigens after transplantation, and early AR [97,98]. These alloreactive T cells can be measured with pretransplantation functional assays (e.g.…”

Section: Biomarkers Predicting Belatacept-resistant Rejectionmentioning

confidence: 99%

“…These alloreactive T cells can be measured with pretransplantation functional assays (e.g. measurement donor-reactive immune cells with enzyme-linked immunosorbent spot [ELISpot]) [97,99]. Several studies have been performed to elucidate the pathogenesis of AR after belatacept therapy.…”

Section: Biomarkers Predicting Belatacept-resistant Rejectionmentioning

confidence: 99%

Costimulation Blockade in Kidney Transplant Recipients

Zwan

Hesselink

Hoogen

et al. 2019

Drugs

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Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.

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Biomarkers to assess donor-reactive T-cell responses in kidney transplant patients

Cited by 13 publications

References 109 publications

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year

Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation

Costimulation Blockade in Kidney Transplant Recipients

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