Dataset Information

Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant.

ABSTRACT:

Introduction

The cellular events that contribute to generation of donor-specific anti-HLA antibodies (DSA) post-kidney transplantation (KTx) are not well understood. Characterization of such mechanisms could allow tailoring of immunosuppression to benefit sensitized patients.

Methods

We prospectively monitored circulating T follicular helper (cT_FH) cells in KTx recipients who received T-cell depleting (thymoglobulin, n = 54) or T-cell nondepleting (basiliximab, n = 20) induction therapy from pre-KTx to 1 year post-KTx and assessed their phenotypic changes due to induction and DSA occurrence, in addition to healthy controls (n = 13), for a total of 307 blood samples.

Results

Before KTx, patients displayed comparable levels of resting, central memory cT_FH cells with similar polarization to those of healthy controls. Unlike basiliximab induction, thymoglobulin induction significantly depleted cT_FH cells, triggered lymphopenia-induced proliferation that skewed cT_FH cells toward increased Th1 polarization, effector memory, and elevated programmed cell death protein 1 (PD-1)^int/hi expression, resembling activated phenotypes. Regardless of induction, patients who developed DSA post-KTx, harbored pre-KTx donor-reactive memory interleukin (IL)-21⁺ cT_FH cells and showed higher % cT_FH and lower % of T regulatory (T_REG) cells post-KTx resulting in elevated cT_FH:T_REG ratio at DSA occurrence.

Conclusion

Induction therapy distinctly shapes cT_FH cell phenotype post-KTx. Monitoring cT_FH cells before and after KTx may help detect those patients prone to DSA generation post-KTx.

SUBMITTER: Macedo C

PROVIDER: S-EPMC6409398 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant.

Macedo Camila C Hadi Kevin K Walters John J Elinoff Beth B Marrari Marilyn M Zeevi Adriana A Ramaswami Bala B Chalasani Geetha G Landsittel Douglas D Shields Adele A Alloway Rita R Lakkis Fadi G FG Woodle E Steve ES Metes Diana D

Kidney international reports 20181208 3

<h4>Introduction</h4>The cellular events that contribute to generation of donor-specific anti-HLA antibodies (DSA) post-kidney transplantation (KTx) are not well understood. Characterization of such mechanisms could allow tailoring of immunosuppression to benefit sensitized patients.<h4>Methods</h4>We prospectively monitored circulating T follicular helper (cT<sub>FH</sub>) cells in KTx recipients who received T-cell depleting (thymoglobulin, <i>n</i> = 54) or T-cell nondepleting (basiliximab, < ...[more]

PMID: 30899873

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Dataset Information

Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant.

Introduction

Methods

Results

Conclusion

Publications

Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant.

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