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)-? concentration. Conclusion:Changes in Th1?cells, EMCD8+ T cells and EBV-specific CD8+ T cells, which coincided with an increase in IFN-?, were significantly different between regressive LPD and persistent LPD after MTX cessation.

SUBMITTER: Saito S 

PROVIDER: S-EPMC5893782 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature