Elsevier

Clinica Chimica Acta

Volume 523, December 2021, Pages 247-259
Clinica Chimica Acta

Lymphocyte function based on IFN-γ secretion assay may be a promising indicator for assessing different immune status in renal transplant recipients

https://doi.org/10.1016/j.cca.2021.10.003Get rights and content

Highlights

  • •

    The method detecting function of lymphocytes is novel in evaluating immune status.

  • •

    Ability of lymphocytes secreting IFN-γ offers a good way for immune status in patients.

  • •

    IFN-r+CD8 & CD4 T% is the best predictor for infection & rejection, respectively.

  • •

    Lymphocyte subsets and function were measured regularly before and after surgery.

  • •

    This project establishes an immune evaluation system of recipients more accurately.

Abstract

Background

Immunological monitoring plays a crucial role in organ recipients for allowing tailoring of immunosuppression. However, there is still a paucity of promising indicators for detecting immune status in recipients.

Methods

We conducted a prospective study to characterize the immune status by detecting dynamically lymphocyte subsets and function (represented by the abilities to secrete IFN-γ) in the first 6 months posttransplant in renal recipients. Participants were classified into an immune stable group, infected group, and rejected group.

Results

In the stable group, our study suggested that the counts and function of CD4+ T, CD8+ T, and NK lymphocytes decreased to their nadir at week 2, and thereafter these indicators were gradually restored. The counts exceeded pre-operative levels, whereas function did not reach the pre-transplant levels by 6 months. We demonstrated that function of lymphocytes was considerably decreased in infected recipients compared with the stable group when infection occurred. By contrast, the function of lymphocytes was obviously increased at the point of rejection. Receiver operating characteristic (ROC) analysis in the combination of subsets and function of lymphocytes presented a superior clinical value with an area under the curve (AUC) of 0.903 in the diagnosis of infected receivers, and IFN-γ+CD8+ T cells% is the highest indicator with the auROC curve of 0.862. Another ROC analysis confirmed that IFN-γ+CD4  T cells% presented a preferable diagnostic value with an area of 0.887 for rejected recipients.

Conclusions

In conclusion, the ability of lymphocyte subsets secreting IFN-γ may provide a promising assessment of immune status in recipients and allow timely modifying immunosuppression.

Section snippets

Background

With the mature application of preoperative positive cross-match and postoperative immunosuppressive therapy, the quality of life and survival of renal grafts and transplant recipients have been greatly improved [1]. However, the long-term outcome of grafts remains a key challenge, and immune factors play a core role in the process [2], [3]. Excessive immunosuppression may lead to various infections or malignancies in transplant recipients, while inadequate immunosuppression may increase the

Study population and blood sample collection

The prospective observational cohort study was conducted at the institute of organ transplantation, Tongji Hospital, Huazhong University of Science and Technology. A total of 158 recipients (≥18 years) undergoing primary kidney transplants from deceased donors or living related donors were enrolled and followed up for an average of 6 months in this study between March 2018 to December 2020. For the sake of minimizing the impact of a variety of complex factors on immune status, recipients were

Baseline characteristics and post-transplant results

In total 158 recipients (median age 48.17 ± 11.41 years, range18-64 years) finally met the criteria, including 64 females (40.51%) and 94 males (59.49%). Clinical characteristics were summarized in Table 1. Changes in lymphocyte subsets (CD4+ T cells, CD8+ T cells, NK cells) and their function (IFN-γ cellular secreting capacity) were monitored dynamically.

The participants were classified into 3 groups according to their postoperative immune status: stable immune status group (no infection or

Discussion

There has been increasing interest in immunological monitoring in solid organ transplant recipients [21], [22], [23], which is helpful to provide a comprehensive and precise assessment of individual’s actual risk of various post-transplant complications, particularly infection and rejection [24], together with allowing tailoring of immunosuppression and prophylaxis practices, as well as minimize the side effects of immunotherapeutic approaches [25], [26]. Nevertheless, the immune status of

Conclusions

In the future, we will conduct a larger cohort with longer follow up to lay a more reliable foundation and criteria for immune surveillance of transplant recipients, so as to further determine the optimal threshold and effectiveness of interventions based on statistical analysis. Validating the data and setting personalized immunosuppressive regimes, we can take proper precautions, such as enhancing anti-infection prevention and precise adjustment of immunosuppression, identifying recipients at

Funding

This work was supported by research grants from National Natural Science Foundation of China (No. 81873511), and the Health and Family Planning Commission of Hubei Province of China (WJ2019Z007).

Data availability statement

All the information generated or analyzed during this study was supplied regarding data availability: The raw measurements are provided in the Supplemental Files.

Disclosure

The authors of this manuscript declare no conflicts of interest to disclose as described by the Clinical and experimental immunology.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (48)

  • M. Fernández-Ruiz et al.

    Clinical immune-monitoring strategies for predicting infection risk in solid organ transplantation

    Clin. Transl. Immunol.

    (2014)
  • P.E. Cippà et al.

    Risk stratification for rejection and infection after kidney transplantation

    Clin. J. American Soc. Nephrol.

    (2015)
  • C. Whiting Chan et al.

    Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging

    PLoS ONE

    (2015)
  • V. Losappio et al.

    Molecular Mechanisms of Premature Aging in Hemodialysis: The Complex Interplay Between Innate and Adaptive Immune Dysfunction

    Int. J. Mol. Sci.

    (2020)
  • K. Sugiyama et al.

    Immune monitoring with a lymphocyte adenosine triphosphate assay in kidney transplant recipients treated with a calcineurin inhibitor

    Exp. Clin. Transplant.

    (2014)
  • G.-C. Maria et al.

    Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM).J Immunother

    Cancer

    (2021)
  • M. Yu et al.

    Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation

    Curr. Drug Metab.

    (2018)
  • Q. Zhuang et al.

    The detailed distribution of T cell subpopulations in immune-stable renal allograft recipients: a single center study

    PeerJ

    (2019 Feb)
  • M.S. Chae et al.

    The impact of serum cytokines in the development of early allograft dysfunction in living donor liver transplantation

    Medicine.

    (2018)
  • M.A. Wood-Trageser et al.

    Enhancing the Value of Histopathological Assessment of Allograft Biopsy Monitoring

    Transplantation

    (2019 Jul)
  • X. Ling et al.

    Can immune cell function assay identify patients at risk of infection or rejection? A meta-analysis

    Transplantation

    (2012)
  • B. Sawitzki et al.

    Can we use biomarkers and functional assays to implement personalized therapies in transplantation?

    Transplantation

    (2009)
  • H. Hou et al.

    Establishment of the Reference Intervals of Lymphocyte Function in Healthy Adults Based on IFN-gamma Secretion Assay upon Phorbol-12-Myristate-13-Acetate/Ionomycin Stimulation

    Front. Immunol.

    (2018)
  • Haas M, Loupy A, Lefaucheur C, et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic...
    • View full text
    © 2021 Elsevier B.V. All rights reserved.