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Posttransplant peripheral blood donor-specific interferon-γ enzyme-linked immune spot assay differentiates risk of subclinical rejection and de novo donor-specific alloantibodies in kidney transplant recipients.
Kidney Int. 2017 07; 92(1):201-213.KI

Abstract

Noninvasive diagnosis of kidney allograft inflammation in transplant recipients with stable graft function (subclinical rejection) could permit more effective therapy and prevent later development of de novo anti-donor HLA antibodies and/or graft dysfunction. Here we tested whether quantifying posttransplant donor-specific alloreactive T-cells by IFN-γ ELISPOT assay noninvasively detects subclinical T-cell mediated rejection and/or predicts development of anti-donor HLA antibodies. Using an initial cross-sectional cohort of 60 kidney transplant patients with six-month surveillance biopsies, we found that negative donor-specific IFN-γ ELISPOT assays accurately ruled out the presence of subclinical T-cell mediated rejection. These results were validated using a distinct prospective cohort of 101 patients where donor-specific IFN-γ ELISPOT results at both three- and six-months posttransplant significantly differentiated patients with subclinical T-cell mediated rejection at six months, independent of other clinical variables (odds ratio 0.072, 95% confidence interval 0.008-0.653). The posttransplant donor-specific IFN-γ ELISPOT results independently associated with subsequent development of significant anti-donor HLA antibodies (0.085, 0.008-0.862) and with significantly worse two-year function (estimated glomerular filtration rate) compared to patients with a negative test. Thus, posttransplant immune monitoring by donor-specific IFN-γ ELISPOT can assess risk for developing subclinical T-cell mediated rejection and anti-donor HLA antibodies, potentially limiting the need for surveillance biopsies. Our study provides a guide for individualizing immunosuppression to improve posttransplant outcomes.

Authors+Show Affiliations

Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain.Renal Division, Department of Medicine and the Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, USA.HLA histocompatibility Laboratory, Hospital Clinic de Barcelona, Barcelona, Spain.Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain.Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain.Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain; Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain.Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain.Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain.Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain.Renal Division, Department of Medicine and the Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, USA.Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain.Pathology Department, Bellvitge University Hospital, Barcelona, Spain.Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain; Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain.Renal Division, Department of Medicine and the Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, USA.Experimental Nephrology Laboratory, IDIBELL, Barcelona University, Barcelona, Spain; Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain. Electronic address: obestard@bellvitgehospital.cat.

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

28274484

Citation

Crespo, Elena, et al. "Posttransplant Peripheral Blood Donor-specific Interferon-γ Enzyme-linked Immune Spot Assay Differentiates Risk of Subclinical Rejection and De Novo Donor-specific Alloantibodies in Kidney Transplant Recipients." Kidney International, vol. 92, no. 1, 2017, pp. 201-213.
Crespo E, Cravedi P, Martorell J, et al. Posttransplant peripheral blood donor-specific interferon-γ enzyme-linked immune spot assay differentiates risk of subclinical rejection and de novo donor-specific alloantibodies in kidney transplant recipients. Kidney Int. 2017;92(1):201-213.
Crespo, E., Cravedi, P., Martorell, J., Luque, S., Melilli, E., Cruzado, J. M., Jarque, M., Meneghini, M., Manonelles, A., Donadei, C., Lloberas, N., Gomà, M., Grinyó, J. M., Heeger, P., & Bestard, O. (2017). Posttransplant peripheral blood donor-specific interferon-γ enzyme-linked immune spot assay differentiates risk of subclinical rejection and de novo donor-specific alloantibodies in kidney transplant recipients. Kidney International, 92(1), 201-213. https://doi.org/10.1016/j.kint.2016.12.024
Crespo E, et al. Posttransplant Peripheral Blood Donor-specific Interferon-γ Enzyme-linked Immune Spot Assay Differentiates Risk of Subclinical Rejection and De Novo Donor-specific Alloantibodies in Kidney Transplant Recipients. Kidney Int. 2017;92(1):201-213. PubMed PMID: 28274484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Posttransplant peripheral blood donor-specific interferon-γ enzyme-linked immune spot assay differentiates risk of subclinical rejection and de novo donor-specific alloantibodies in kidney transplant recipients. AU - Crespo,Elena, AU - Cravedi,Paolo, AU - Martorell,Jaume, AU - Luque,Sergi, AU - Melilli,Edoardo, AU - Cruzado,Josep M, AU - Jarque,Marta, AU - Meneghini,Maria, AU - Manonelles,Anna, AU - Donadei,Chiara, AU - Lloberas,Núria, AU - Gomà,Montse, AU - Grinyó,Josep M, AU - Heeger,Peter, AU - Bestard,Oriol, Y1 - 2017/03/06/ PY - 2016/08/11/received PY - 2016/12/09/revised PY - 2016/12/15/accepted PY - 2017/3/10/pubmed PY - 2018/4/4/medline PY - 2017/3/10/entrez KW - T-cell alloreactivity KW - de novo alloantibodies KW - kidney transplantation KW - noninvasive biomarkers SP - 201 EP - 213 JF - Kidney international JO - Kidney Int. VL - 92 IS - 1 N2 - Noninvasive diagnosis of kidney allograft inflammation in transplant recipients with stable graft function (subclinical rejection) could permit more effective therapy and prevent later development of de novo anti-donor HLA antibodies and/or graft dysfunction. Here we tested whether quantifying posttransplant donor-specific alloreactive T-cells by IFN-γ ELISPOT assay noninvasively detects subclinical T-cell mediated rejection and/or predicts development of anti-donor HLA antibodies. Using an initial cross-sectional cohort of 60 kidney transplant patients with six-month surveillance biopsies, we found that negative donor-specific IFN-γ ELISPOT assays accurately ruled out the presence of subclinical T-cell mediated rejection. These results were validated using a distinct prospective cohort of 101 patients where donor-specific IFN-γ ELISPOT results at both three- and six-months posttransplant significantly differentiated patients with subclinical T-cell mediated rejection at six months, independent of other clinical variables (odds ratio 0.072, 95% confidence interval 0.008-0.653). The posttransplant donor-specific IFN-γ ELISPOT results independently associated with subsequent development of significant anti-donor HLA antibodies (0.085, 0.008-0.862) and with significantly worse two-year function (estimated glomerular filtration rate) compared to patients with a negative test. Thus, posttransplant immune monitoring by donor-specific IFN-γ ELISPOT can assess risk for developing subclinical T-cell mediated rejection and anti-donor HLA antibodies, potentially limiting the need for surveillance biopsies. Our study provides a guide for individualizing immunosuppression to improve posttransplant outcomes. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/28274484/Posttransplant_peripheral_blood_donor_specific_interferon_γ_enzyme_linked_immune_spot_assay_differentiates_risk_of_subclinical_rejection_and_de_novo_donor_specific_alloantibodies_in_kidney_transplant_recipients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(17)30017-0 DB - PRIME DP - Unbound Medicine ER -