Restoration of decreased T helper 1 and CD8+ T cell subsets is associated with regression of lymphoproliferative disorders developed during methotrexate treatment

Shuntaro Saito, Katsuya Suzuki, Keiko Yoshimoto, Yuko Kaneko, Kunihiro Yamaoka, Takayuki Shimizu, Takehiko Mori, Shinichiro Okamoto, Kaori Kameyama, Koichi Amano, Jun Ichi Tamaru, Michihide Tokuhira, Tsutomu Takeuchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Lymphoproliferative disorder (LPD), including malignant lymphoma, is a relatively rare but life-threatening complication in RA patients under methotrexate (MTX) therapy. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct characteristic in part of such LPDs. Objective: The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD. Methods: We studied RA patients who developed LPD during MTX administration (n = 35) and clinically matched controls (n = 35). The time of MTX cessation was defined as week 0, and LPD patients were divided into two groups according to LPD status at week 12: regressive group (n = 22) and persistent group (n = 13). Flow cytometric analysis of whole blood samples and serum cytokine assays were conducted for LPD (n = 10) and control patients (n = 10) at weeks 0, 4, and 12. Results: There was a significant decrease in peripheral lymphocytes and the proportion of T helper 1 cells (Th1 cells), effector memory CD8+ T cells (EMCD8+ T) and Epstein-Barr virus (EBV)-specific CD8+ T cells at the time of LPD diagnosis, and a significant increase after MTX cessation was observed in the regressive group but not in the persistent group. The expansion of Th1 cells and EMCD8+ T cells significantly correlated with an increase in serum interferon (IFN)-γ concentration. Conclusion: Changes in Th1 cells, EMCD8+ T cells and EBV-specific CD8+ T cells, which coincided with an increase in IFN-γ, were significantly different between regressive LPD and persistent LPD after MTX cessation.

Original languageEnglish
Article number621
JournalFrontiers in Immunology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - 2018 Apr 4

Fingerprint

Lymphoproliferative Disorders
T-Lymphocyte Subsets
Methotrexate
Th1 Cells
T-Lymphocytes
Therapeutics
Human Herpesvirus 4
Interferons
Serum
Lymphoma
Lymphocytes
Cytokines

Keywords

  • Lymphoproliferative disorder
  • Malignant lymphoma
  • Methotrexate
  • Regression
  • T cell subset

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{a08eb3a6989f4a9c9fbe42f617993bb5,
title = "Restoration of decreased T helper 1 and CD8+ T cell subsets is associated with regression of lymphoproliferative disorders developed during methotrexate treatment",
abstract = "Background: Lymphoproliferative disorder (LPD), including malignant lymphoma, is a relatively rare but life-threatening complication in RA patients under methotrexate (MTX) therapy. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct characteristic in part of such LPDs. Objective: The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD. Methods: We studied RA patients who developed LPD during MTX administration (n = 35) and clinically matched controls (n = 35). The time of MTX cessation was defined as week 0, and LPD patients were divided into two groups according to LPD status at week 12: regressive group (n = 22) and persistent group (n = 13). Flow cytometric analysis of whole blood samples and serum cytokine assays were conducted for LPD (n = 10) and control patients (n = 10) at weeks 0, 4, and 12. Results: There was a significant decrease in peripheral lymphocytes and the proportion of T helper 1 cells (Th1 cells), effector memory CD8+ T cells (EMCD8+ T) and Epstein-Barr virus (EBV)-specific CD8+ T cells at the time of LPD diagnosis, and a significant increase after MTX cessation was observed in the regressive group but not in the persistent group. The expansion of Th1 cells and EMCD8+ T cells significantly correlated with an increase in serum interferon (IFN)-γ concentration. Conclusion: Changes in Th1 cells, EMCD8+ T cells and EBV-specific CD8+ T cells, which coincided with an increase in IFN-γ, were significantly different between regressive LPD and persistent LPD after MTX cessation.",
keywords = "Lymphoproliferative disorder, Malignant lymphoma, Methotrexate, Regression, T cell subset",
author = "Shuntaro Saito and Katsuya Suzuki and Keiko Yoshimoto and Yuko Kaneko and Kunihiro Yamaoka and Takayuki Shimizu and Takehiko Mori and Shinichiro Okamoto and Kaori Kameyama and Koichi Amano and Tamaru, {Jun Ichi} and Michihide Tokuhira and Tsutomu Takeuchi",
year = "2018",
month = "4",
day = "4",
doi = "10.3389/fimmu.2018.00621",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "APR",

}

TY - JOUR

T1 - Restoration of decreased T helper 1 and CD8+ T cell subsets is associated with regression of lymphoproliferative disorders developed during methotrexate treatment

AU - Saito, Shuntaro

AU - Suzuki, Katsuya

AU - Yoshimoto, Keiko

AU - Kaneko, Yuko

AU - Yamaoka, Kunihiro

AU - Shimizu, Takayuki

AU - Mori, Takehiko

AU - Okamoto, Shinichiro

AU - Kameyama, Kaori

AU - Amano, Koichi

AU - Tamaru, Jun Ichi

AU - Tokuhira, Michihide

AU - Takeuchi, Tsutomu

PY - 2018/4/4

Y1 - 2018/4/4

N2 - Background: Lymphoproliferative disorder (LPD), including malignant lymphoma, is a relatively rare but life-threatening complication in RA patients under methotrexate (MTX) therapy. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct characteristic in part of such LPDs. Objective: The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD. Methods: We studied RA patients who developed LPD during MTX administration (n = 35) and clinically matched controls (n = 35). The time of MTX cessation was defined as week 0, and LPD patients were divided into two groups according to LPD status at week 12: regressive group (n = 22) and persistent group (n = 13). Flow cytometric analysis of whole blood samples and serum cytokine assays were conducted for LPD (n = 10) and control patients (n = 10) at weeks 0, 4, and 12. Results: There was a significant decrease in peripheral lymphocytes and the proportion of T helper 1 cells (Th1 cells), effector memory CD8+ T cells (EMCD8+ T) and Epstein-Barr virus (EBV)-specific CD8+ T cells at the time of LPD diagnosis, and a significant increase after MTX cessation was observed in the regressive group but not in the persistent group. The expansion of Th1 cells and EMCD8+ T cells significantly correlated with an increase in serum interferon (IFN)-γ concentration. Conclusion: Changes in Th1 cells, EMCD8+ T cells and EBV-specific CD8+ T cells, which coincided with an increase in IFN-γ, were significantly different between regressive LPD and persistent LPD after MTX cessation.

AB - Background: Lymphoproliferative disorder (LPD), including malignant lymphoma, is a relatively rare but life-threatening complication in RA patients under methotrexate (MTX) therapy. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct characteristic in part of such LPDs. Objective: The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD. Methods: We studied RA patients who developed LPD during MTX administration (n = 35) and clinically matched controls (n = 35). The time of MTX cessation was defined as week 0, and LPD patients were divided into two groups according to LPD status at week 12: regressive group (n = 22) and persistent group (n = 13). Flow cytometric analysis of whole blood samples and serum cytokine assays were conducted for LPD (n = 10) and control patients (n = 10) at weeks 0, 4, and 12. Results: There was a significant decrease in peripheral lymphocytes and the proportion of T helper 1 cells (Th1 cells), effector memory CD8+ T cells (EMCD8+ T) and Epstein-Barr virus (EBV)-specific CD8+ T cells at the time of LPD diagnosis, and a significant increase after MTX cessation was observed in the regressive group but not in the persistent group. The expansion of Th1 cells and EMCD8+ T cells significantly correlated with an increase in serum interferon (IFN)-γ concentration. Conclusion: Changes in Th1 cells, EMCD8+ T cells and EBV-specific CD8+ T cells, which coincided with an increase in IFN-γ, were significantly different between regressive LPD and persistent LPD after MTX cessation.

KW - Lymphoproliferative disorder

KW - Malignant lymphoma

KW - Methotrexate

KW - Regression

KW - T cell subset

UR - http://www.scopus.com/inward/record.url?scp=85045019951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045019951&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2018.00621

DO - 10.3389/fimmu.2018.00621

M3 - Article

AN - SCOPUS:85045019951

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - APR

M1 - 621

ER -