T Cell Subset Profile and Appearance of Donor-specific Antibodies in Primary and Retransplanted Kidney Recipients

B. Nemes, Aliz Barta, Gergely Ivádi, Bettina Kárai, Eszter Szánthó, Zsuzsa Hevessy, Réka P. Szabó, Anikó Szilvási, Sándor Sipka, S. Baráth

Research output: Contribution to journalArticle

Abstract

Introduction: Accelerated antibody-mediated rejection is a major challenge after kidney transplantation. While the clinical course, diagnosis, and treatment of cell-mediated acute rejection is agreed upon and has been successfully performed, the antibody-mediated rejection remains a problem. Biopsies cannot be repeated several times, are not always representative, and are refused by many patients. Analysis of T-cell subsets and donor-specific antibodies (DSAs)might be an additive diagnostic tool in the case of kidney transplantation. Method: Between 2015 and 2017, 50 kidney transplant patients were enrolled in the study. Patients were divided into 2 clinical groups: primary transplants and regrafted patients. Serum samples were collected right before the operation, then in 1 week; 30, 60, and 180 days; and yearly. Besides routine laboratory, multicolor flow cytometry was performed for T cell subsets, and Luminex Single Antigen Bead assay for the detection on donor-specific anti-HLA antibodies. Medical data were also fixed. Results: The percentage of CD4+ and CD8+ cells (the CD4+/CD8+ rate)did not change much over time in either group. The percentage of CD19+ cells increased until week 1, then decreased back to its original level by day 180. CD56+/3-% was high in both groups and had no characteristic kinetics by the time. The CD4+ naïve absolute cell count increased in first-time transplants and did not decreased back to its original value until the end of year 1. This is in contrast to retransplants, where CD4+ naïve cell count rapidly dropped below its original value and remained low throughout the first year after transplantation. The CD8+ effector memory absolute cell-count was higher in first-time transplants compared to retransplanted patients in all time points. By the end of month 1, the CD19+ naïve absolute cell-count increased in first-time transplants to 170% of its original value; however, it remained or decreased in second transplants. By the end of the first year, the CD19+ naïve absolute cell count diminished to 70% in first-time transplants and 38% in second transplants. DSA was detected in 9 out of the 38 first-time transplants (23.7%)compared to 7 out of 12 (58.3%)in regrafted patients during the observational period (P =.001). It was typical for regrafted patients for DSAs to appear earlier after transplantation, and that more simultaneously different antibodies were detected against more antigens at the first time point compared to first-time transplants. Discussion: The 2 groups were similar in demographics and there were no differences regarding the clinical course, complications, or output data. However, we found statistical differences regarding the dynamics of T cell subsets and DSAs. The parallel measurement of CD subsets and DSAs might be a sensitive and useful additive tool in diagnosing subclinical immunologic changes after transplantation.

Original languageEnglish
Pages (from-to)1215-1225
Number of pages11
JournalTransplantation Proceedings
Volume51
Issue number4
DOIs
Publication statusPublished - May 1 2019

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T-Lymphocyte Subsets
Tissue Donors
Transplants
Kidney
Antibodies
Cell Count
Transplantation
Kidney Transplantation
Antigens
CD4 Lymphocyte Count
Anti-Idiotypic Antibodies
Flow Cytometry
Demography
Biopsy

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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T Cell Subset Profile and Appearance of Donor-specific Antibodies in Primary and Retransplanted Kidney Recipients. / Nemes, B.; Barta, Aliz; Ivádi, Gergely; Kárai, Bettina; Szánthó, Eszter; Hevessy, Zsuzsa; Szabó, Réka P.; Szilvási, Anikó; Sipka, Sándor; Baráth, S.

In: Transplantation Proceedings, Vol. 51, No. 4, 01.05.2019, p. 1215-1225.

Research output: Contribution to journalArticle

Nemes, B. ; Barta, Aliz ; Ivádi, Gergely ; Kárai, Bettina ; Szánthó, Eszter ; Hevessy, Zsuzsa ; Szabó, Réka P. ; Szilvási, Anikó ; Sipka, Sándor ; Baráth, S. / T Cell Subset Profile and Appearance of Donor-specific Antibodies in Primary and Retransplanted Kidney Recipients. In: Transplantation Proceedings. 2019 ; Vol. 51, No. 4. pp. 1215-1225.
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abstract = "Introduction: Accelerated antibody-mediated rejection is a major challenge after kidney transplantation. While the clinical course, diagnosis, and treatment of cell-mediated acute rejection is agreed upon and has been successfully performed, the antibody-mediated rejection remains a problem. Biopsies cannot be repeated several times, are not always representative, and are refused by many patients. Analysis of T-cell subsets and donor-specific antibodies (DSAs)might be an additive diagnostic tool in the case of kidney transplantation. Method: Between 2015 and 2017, 50 kidney transplant patients were enrolled in the study. Patients were divided into 2 clinical groups: primary transplants and regrafted patients. Serum samples were collected right before the operation, then in 1 week; 30, 60, and 180 days; and yearly. Besides routine laboratory, multicolor flow cytometry was performed for T cell subsets, and Luminex Single Antigen Bead assay for the detection on donor-specific anti-HLA antibodies. Medical data were also fixed. Results: The percentage of CD4+ and CD8+ cells (the CD4+/CD8+ rate)did not change much over time in either group. The percentage of CD19+ cells increased until week 1, then decreased back to its original level by day 180. CD56+/3-{\%} was high in both groups and had no characteristic kinetics by the time. The CD4+ na{\"i}ve absolute cell count increased in first-time transplants and did not decreased back to its original value until the end of year 1. This is in contrast to retransplants, where CD4+ na{\"i}ve cell count rapidly dropped below its original value and remained low throughout the first year after transplantation. The CD8+ effector memory absolute cell-count was higher in first-time transplants compared to retransplanted patients in all time points. By the end of month 1, the CD19+ na{\"i}ve absolute cell-count increased in first-time transplants to 170{\%} of its original value; however, it remained or decreased in second transplants. By the end of the first year, the CD19+ na{\"i}ve absolute cell count diminished to 70{\%} in first-time transplants and 38{\%} in second transplants. DSA was detected in 9 out of the 38 first-time transplants (23.7{\%})compared to 7 out of 12 (58.3{\%})in regrafted patients during the observational period (P =.001). It was typical for regrafted patients for DSAs to appear earlier after transplantation, and that more simultaneously different antibodies were detected against more antigens at the first time point compared to first-time transplants. Discussion: The 2 groups were similar in demographics and there were no differences regarding the clinical course, complications, or output data. However, we found statistical differences regarding the dynamics of T cell subsets and DSAs. The parallel measurement of CD subsets and DSAs might be a sensitive and useful additive tool in diagnosing subclinical immunologic changes after transplantation.",
author = "B. Nemes and Aliz Barta and Gergely Iv{\'a}di and Bettina K{\'a}rai and Eszter Sz{\'a}nth{\'o} and Zsuzsa Hevessy and Szab{\'o}, {R{\'e}ka P.} and Anik{\'o} Szilv{\'a}si and S{\'a}ndor Sipka and S. Bar{\'a}th",
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TY - JOUR

T1 - T Cell Subset Profile and Appearance of Donor-specific Antibodies in Primary and Retransplanted Kidney Recipients

AU - Nemes, B.

AU - Barta, Aliz

AU - Ivádi, Gergely

AU - Kárai, Bettina

AU - Szánthó, Eszter

AU - Hevessy, Zsuzsa

AU - Szabó, Réka P.

AU - Szilvási, Anikó

AU - Sipka, Sándor

AU - Baráth, S.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Introduction: Accelerated antibody-mediated rejection is a major challenge after kidney transplantation. While the clinical course, diagnosis, and treatment of cell-mediated acute rejection is agreed upon and has been successfully performed, the antibody-mediated rejection remains a problem. Biopsies cannot be repeated several times, are not always representative, and are refused by many patients. Analysis of T-cell subsets and donor-specific antibodies (DSAs)might be an additive diagnostic tool in the case of kidney transplantation. Method: Between 2015 and 2017, 50 kidney transplant patients were enrolled in the study. Patients were divided into 2 clinical groups: primary transplants and regrafted patients. Serum samples were collected right before the operation, then in 1 week; 30, 60, and 180 days; and yearly. Besides routine laboratory, multicolor flow cytometry was performed for T cell subsets, and Luminex Single Antigen Bead assay for the detection on donor-specific anti-HLA antibodies. Medical data were also fixed. Results: The percentage of CD4+ and CD8+ cells (the CD4+/CD8+ rate)did not change much over time in either group. The percentage of CD19+ cells increased until week 1, then decreased back to its original level by day 180. CD56+/3-% was high in both groups and had no characteristic kinetics by the time. The CD4+ naïve absolute cell count increased in first-time transplants and did not decreased back to its original value until the end of year 1. This is in contrast to retransplants, where CD4+ naïve cell count rapidly dropped below its original value and remained low throughout the first year after transplantation. The CD8+ effector memory absolute cell-count was higher in first-time transplants compared to retransplanted patients in all time points. By the end of month 1, the CD19+ naïve absolute cell-count increased in first-time transplants to 170% of its original value; however, it remained or decreased in second transplants. By the end of the first year, the CD19+ naïve absolute cell count diminished to 70% in first-time transplants and 38% in second transplants. DSA was detected in 9 out of the 38 first-time transplants (23.7%)compared to 7 out of 12 (58.3%)in regrafted patients during the observational period (P =.001). It was typical for regrafted patients for DSAs to appear earlier after transplantation, and that more simultaneously different antibodies were detected against more antigens at the first time point compared to first-time transplants. Discussion: The 2 groups were similar in demographics and there were no differences regarding the clinical course, complications, or output data. However, we found statistical differences regarding the dynamics of T cell subsets and DSAs. The parallel measurement of CD subsets and DSAs might be a sensitive and useful additive tool in diagnosing subclinical immunologic changes after transplantation.

AB - Introduction: Accelerated antibody-mediated rejection is a major challenge after kidney transplantation. While the clinical course, diagnosis, and treatment of cell-mediated acute rejection is agreed upon and has been successfully performed, the antibody-mediated rejection remains a problem. Biopsies cannot be repeated several times, are not always representative, and are refused by many patients. Analysis of T-cell subsets and donor-specific antibodies (DSAs)might be an additive diagnostic tool in the case of kidney transplantation. Method: Between 2015 and 2017, 50 kidney transplant patients were enrolled in the study. Patients were divided into 2 clinical groups: primary transplants and regrafted patients. Serum samples were collected right before the operation, then in 1 week; 30, 60, and 180 days; and yearly. Besides routine laboratory, multicolor flow cytometry was performed for T cell subsets, and Luminex Single Antigen Bead assay for the detection on donor-specific anti-HLA antibodies. Medical data were also fixed. Results: The percentage of CD4+ and CD8+ cells (the CD4+/CD8+ rate)did not change much over time in either group. The percentage of CD19+ cells increased until week 1, then decreased back to its original level by day 180. CD56+/3-% was high in both groups and had no characteristic kinetics by the time. The CD4+ naïve absolute cell count increased in first-time transplants and did not decreased back to its original value until the end of year 1. This is in contrast to retransplants, where CD4+ naïve cell count rapidly dropped below its original value and remained low throughout the first year after transplantation. The CD8+ effector memory absolute cell-count was higher in first-time transplants compared to retransplanted patients in all time points. By the end of month 1, the CD19+ naïve absolute cell-count increased in first-time transplants to 170% of its original value; however, it remained or decreased in second transplants. By the end of the first year, the CD19+ naïve absolute cell count diminished to 70% in first-time transplants and 38% in second transplants. DSA was detected in 9 out of the 38 first-time transplants (23.7%)compared to 7 out of 12 (58.3%)in regrafted patients during the observational period (P =.001). It was typical for regrafted patients for DSAs to appear earlier after transplantation, and that more simultaneously different antibodies were detected against more antigens at the first time point compared to first-time transplants. Discussion: The 2 groups were similar in demographics and there were no differences regarding the clinical course, complications, or output data. However, we found statistical differences regarding the dynamics of T cell subsets and DSAs. The parallel measurement of CD subsets and DSAs might be a sensitive and useful additive tool in diagnosing subclinical immunologic changes after transplantation.

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