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Involvement of Epstein-Barr virus in the development and spontaneous regression of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis


1, 2, 3, 4, 5, 6

 

  1. Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. kitamura.noboru@nihon-u.ac.jp
  2. Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
  3. Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
  4. Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
  5. Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
  6. Division of Haematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

CER14569
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PMID: 34369356 [PubMed]

Received: 26/02/2021
Accepted : 12/07/2021
In Press: 05/08/2021

Abstract

OBJECTIVES:
Conventionally, some patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) undergo spontaneous tumour regression after cessation of MTX. Although the involvement of Epstein-Barr virus (EBV) in the development and spontaneous regression has been suggested, the underlying mechanism remains unknown. In this study, we analysed patients who had developed MTX-LPD to evaluate the association between the development and spontaneous regression of MTX-LPD with EBV.
METHODS:
We analysed the age, stage, disease activity, MTX dose, lymphocyte count, EBV real-time polymerase chain reaction (PCR) test value, and EBV-encoded small RNA (EBER) positivity rate in patients with MTX-LPD at our hospital. Moreover, we investigated the factors related to spontaneous regression, which is a characteristic of MTX-LPD.
RESULTS:
Thirty-four patients were enrolled in this study. The MTX dose at LPD onset was 8.3±2.0 mg/week, and the total dose of MTX was 1,530.3±779.2 mg. The EBV load in the peripheral blood was 270.4±431.8 copy/μL, and the pathological tissues of 17 of 34 (50%) patients tested positive for EBER. Twenty-one patients had spontaneous regression after discontinuation of MTX. The factors related to spontaneous regression were examined using a univariate analysis, and the EBV real-time PCR test value in the peripheral blood, EBER in pathological tissues, and improvement rate of lymphocyte count were considered significant factors. The EBV real-time PCR test value in the peripheral blood was defined as an independent factor of spontaneous regression using a multivariate analysis of related factors.
CONCLUSIONS:
EBV may be involved in the development of MTX-LPD and its spontaneous regression.

Rheumatology Article