Elsevier

Transplant Immunology

Volume 58, February 2020, 101249
Transplant Immunology

Profiles of B-cell subsets in immunologically stable renal allograft recipients and end-stage renal disease patients

https://doi.org/10.1016/j.trim.2019.101249Get rights and content

Highlights

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    Multi-color flow cytometric panel analysis for B cells and their B-cell subsets

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    Comparison of B-cell subsets profiles among ESRD, immunologically stable renal transplant patients and healthy volunteers

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    Single-cell mRNA sequencing to test and analyze the function of B cells.

Abstract

Background

Post-transplantation pharmacotherapies typically employ combinations of immunosuppressive agents that have been designed for targeted inhibition of T-cells and T-cell subsets. Studies of acute and chronic effects of clinically employed immunosuppressive agents on B-cells and B-cell subsets are significantly fewer in number and warrant further investigation. Accordingly, the goal of the present cross-sectional study is to functionally evaluate differences of B-cell subsets in patients with end-stage renal disease (ESRD) and immunologically stable renal transplant patients.

Patients and methods

Of 103 patients who underwent renal transplantation, 73 patients were immunologically stable without rejection or infection. Among them, 34 patients were one-year post-transplantation, and 39 patients were five-year post-transplantation. The study also included 35 ESRD patients and 36 healthy volunteers. Flow cytometry identified B-cell subsets in the study groups.

Results

Renal allograft recipients had reduced percentages of total B-cells (CD19+) and regulatory B-cells (Breg) (CD38highCD27 + CD24+) compared with healthy controls. The percentage of transitional B-cells (IgM + CD38highCD24high) and marginal zone (MZ) B-cells (IgD-CD27+) was reduced in transplant recipients compared with patients with ESRD and healthy volunteers. The highest percentage of plasma cells (PCs) (CD38highCD27 + CD24-) was in patients with ESRD. In five-year post-transplantation group, CD38lowCD21- B-cells increased when compared with the other groups. Healthy volunteers and patients with ESRD had fewer unswitched memory (UM) B-cells (IgM + IgD + CD38lowCD27+), and increased isotype switched memory (ISM) B-cells (IgM-IgD-CD38lowCD27+). There was no difference in the percentage of naïve B-cells (IgD + CD27-) among diverse groups.

Conclusions

The percentages of the total, transitional, Breg, PCs, MZ, and UM B-cell subsets in immunologically stable renal allograft recipients were significantly different from healthy controls. However, B-cell subsets in patients with ESRD were minimally different with immunologically stable renal allograft recipients.

Section snippets

Background

Renal transplantation represents the preeminent life-saving treatment for patients with end-stage renal disease (ESRD) [1]. Post-surgical standards of clinical care focus on pharmacological regimens of immunosuppressive agents to avoid organ rejection [2]. Severe complications of immunosuppressive therapy often include opportunistic infection [3], thereby necessitating continuous monitoring and adjustment of dosages of pharmacological agents linked to efficacious immunological surveillance [4,5

Study population and collection of blood samples

The study population included 103 renal transplant recipients aged 18–65 years who underwent renal transplantation between 1st January 2012 and 31st December 2016 with regular clinical follow-up at the 3rd Xiangya Hospital of Central South University. The study protocol and design were reviewed and approved by the institutional review board (IRB) and Ethics Committee of the 3rd Xiangya Hospital of Central South University (IRB No: 2018-S347) and written informed consent was obtained from every

Baseline patient demographic characteristics

The study included 73 patients who underwent renal transplantation who were immunologically stable without rejection or infection, 35 patients with ESRD, and 36 healthy volunteers. Of the 73 renal transplant recipients, 34 patients were one-year post-transplantation, and 39 patients were five-year post-transplantation. The baseline demographic characteristics of each group are shown in Table 3. The patients in five-year group had an increased average age (44.61 ± 10.53 years old) compared with

Discussion

The overall goal of the present cross-sectional study was to provide detailed data sets and functionally evaluate differences in B-cell subpopulations in immunologically stable renal transplant patients in comparison to ESRD patients and healthy control subjects. The flow cytometry methodology used for analysis of peripheral blood-derived B-cell populations utilized multi-color, predetermined antibody panels to provide selective semi-quantitative profiles of complex cellular arrays. The study

Conclusions

This study, conducted at a single center, included a comprehensive evaluation of the profiles of B-cell subpopulations in patients with end-stage renal disease (ESRD), renal allograft recipients with stable immunity, and showed that the distribution of most B-cell subpopulations in patients with ESRD and immune-stable renal allograft recipients were significantly different from those of healthy controls. These populations were identified using flow cytometry as total B-cells (CD19+), plasma

Source of support

This study was supported by grants from the National Natural Science Foundation of China (81700658 and 81771722), the Natural Science Foundation of Hunan Province (2016JJ4105), the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University (JY201629), and the University Student Innovation Program of Central South University (ZY20180983 and ZY20180988).

Declaration of Competing Interest

None.

Acknowledgments

We wish to note the administrative assistance provided by Mr. Albert Kim.

References (39)

  • M. Matsumoto et al.

    Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation

    Immunity

    (2014)
  • P.E. Zerra et al.

    Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A

    Blood.

    (2017)
  • S. Parajuli et al.

    Characteristics and outcomes of kidney transplant recipients with a functioning graft for more than 25 years

    Kidney Dis (Basel)

    (2018)
  • J.A. Fishman

    Opportunistic infections--coming to the limits of immunosuppression?

    Cold Spring Harb. Perspect. Med.

    (2013)
  • P.E. Cippa et al.

    Risk stratification for rejection and infection after kidney transplantation

    Clin. J. Am. Soc. Nephrol.

    (2015)
  • W. Hoffman et al.

    B cells, antibodies, and more

    Clin. J. Am. Soc. Nephrol.

    (2016)
  • D.A. Kaminski et al.

    Advances in human B cell phenotypic profiling

    Front. Immunol.

    (2012)
  • B. Peng et al.

    Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation

    Cell Death Dis.

    (2018)
  • G.A. Bohmig et al.

    The therapeutic challenge of late antibody-mediated kidney allograft rejection

    Transpl. Int.

    (2019)
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