Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation.
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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200696&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850229283281174528 |
|---|---|
| author | Ilaria Gandolfini Elena Crespo Mukta Baweja Marta Jarque Chiara Donadei Sergio Luque Núria Montero Anna Allesina Laura Perin Umberto Maggiore Paolo Cravedi Oriol Bestard |
| author_facet | Ilaria Gandolfini Elena Crespo Mukta Baweja Marta Jarque Chiara Donadei Sergio Luque Núria Montero Anna Allesina Laura Perin Umberto Maggiore Paolo Cravedi Oriol Bestard |
| author_sort | Ilaria Gandolfini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-efd2f655be7c49e8ac4e45228bb2f3e6 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-efd2f655be7c49e8ac4e45228bb2f3e62025-08-20T02:04:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e020069610.1371/journal.pone.0200696Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation.Ilaria GandolfiniElena CrespoMukta BawejaMarta JarqueChiara DonadeiSergio LuqueNúria MonteroAnna AllesinaLaura PerinUmberto MaggiorePaolo CravediOriol BestardDonor-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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200696&type=printable |
| spellingShingle | Ilaria Gandolfini Elena Crespo Mukta Baweja Marta Jarque Chiara Donadei Sergio Luque Núria Montero Anna Allesina Laura Perin Umberto Maggiore Paolo Cravedi Oriol Bestard Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation. PLoS ONE |
| title | Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation. |
| title_full | Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation. |
| title_fullStr | Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation. |
| title_full_unstemmed | Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation. |
| title_short | Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation. |
| title_sort | impact of preformed t cell alloreactivity by means of donor specific and panel of reactive t cells prt elispot in kidney transplantation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0200696&type=printable |
| work_keys_str_mv | AT ilariagandolfini impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT elenacrespo impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT muktabaweja impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT martajarque impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT chiaradonadei impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT sergioluque impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT nuriamontero impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT annaallesina impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT lauraperin impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT umbertomaggiore impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT paolocravedi impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation AT oriolbestard impactofpreformedtcellalloreactivitybymeansofdonorspecificandpanelofreactivetcellsprtelispotinkidneytransplantation |