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

TITLE=Restoration of Decreased T Helper 1 and CD8+ T Cell Subsets Is Associated With Regression of Lymphoproliferative Disorders Developed During Methotrexate Treatment

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00621

DOI=10.3389/fimmu.2018.00621

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>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.</p></sec><sec id="ST2"><title>Objective</title><p>The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD.</p></sec><sec id="ST3"><title>Methods</title><p>We studied RA patients who developed LPD during MTX administration (<italic>n</italic> = 35) and clinically matched controls (<italic>n</italic> = 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 (<italic>n</italic> = 22) and persistent group (<italic>n</italic> = 13). Flow cytometric analysis of whole blood samples and serum cytokine assays were conducted for LPD (<italic>n</italic> = 10) and control patients (<italic>n</italic> = 10) at weeks 0, 4, and 12.</p></sec><sec id="ST4"><title>Results</title><p>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.</p></sec><sec id="ST5"><title>Conclusion</title><p>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.</p></sec>