Mature T/NK-cell lymphoproliferative disease and Epstein-Barr virus infection are more frequent in patients with rheumatoid arthritis treated with methotrexate

Seiji Kondo, Kazuki Tanimoto, Kozue Yamada, Goichi Yoshimoto, Eiichi Suematsu, Tomoaki Fujisaki, Yumi Oshiro, Kazuo Tamura, Morishige Takeshita, Seiichi Okamura

Research output: Contribution to journalArticle

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Abstract

We retrospectively analyzed in 54 consecutively enrolled Japanese patients with rheumatoid arthritis (RA) and lymphoproliferative disease (LPD) relevant clinicopathological characteristics, in particular paying attention to treatment with methotrexate (MTX). Between the 28 patients treated with MTX (MTX-treated group) and the 26 who were not (non-MTX group), there was no difference in age, interval between onset of RA and LPD, and lymphoma stage. Immunohistochemical analysis showed that in the MTX-treated group, 15 (53 %) patients had mature B-cell LPD, eight (29 %) mature T/NK-cell LPD, and five (18 %) had Hodgkin lymphoma. In the non-MTX group, 22 (84 %) had mature B-cell LPD, 2 (8 %) had mature T/NK-cell LPD, and 2 (8 %) had Hodgkin lymphoma. The frequency of mature T/NK-cell LPD was significantly higher in the MTX-treated group (p < 0.05). Of the eight patients in the MTX-treated group with mature T/NK-cell LPD, two had large granular lymphocytic leukemia and the other six had a variety of different histological types with frequent CD8 but not CD56 expression. Epstein-Barr virus (EBV) infection was significantly higher in the MTX-treated group (p < 0.05); evidence of latent type II EBV infection was found in four of the eight patients with mature T/NK-cell LPD. Withdrawal of MTX led to complete remission in seven patients with mature T/NK-cell LPD irrespective of EBV infection. Our findings highlight that mature T/NK-cell LPD is a frequent complication in RA patients treated with MTX. EBV infection may play a role in the pathogenesis of T/NK-cell LPD, as well as B-cell LPD and Hodgkin lymphoma in MTX-treated RA patients.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalVirchows Archiv
Volume462
Issue number4
DOIs
Publication statusPublished - Apr 1 2013
Externally publishedYes

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Epstein-Barr Virus Infections
Methotrexate
Natural Killer Cells
Rheumatoid Arthritis
Hodgkin Disease
B-Lymphocytes
Large Granular Lymphocytic Leukemia
Lymphoma

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Mature T/NK-cell lymphoproliferative disease and Epstein-Barr virus infection are more frequent in patients with rheumatoid arthritis treated with methotrexate. / Kondo, Seiji; Tanimoto, Kazuki; Yamada, Kozue; Yoshimoto, Goichi; Suematsu, Eiichi; Fujisaki, Tomoaki; Oshiro, Yumi; Tamura, Kazuo; Takeshita, Morishige; Okamura, Seiichi.

In: Virchows Archiv, Vol. 462, No. 4, 01.04.2013, p. 399-407.

Research output: Contribution to journalArticle

Kondo, Seiji ; Tanimoto, Kazuki ; Yamada, Kozue ; Yoshimoto, Goichi ; Suematsu, Eiichi ; Fujisaki, Tomoaki ; Oshiro, Yumi ; Tamura, Kazuo ; Takeshita, Morishige ; Okamura, Seiichi. / Mature T/NK-cell lymphoproliferative disease and Epstein-Barr virus infection are more frequent in patients with rheumatoid arthritis treated with methotrexate. In: Virchows Archiv. 2013 ; Vol. 462, No. 4. pp. 399-407.
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abstract = "We retrospectively analyzed in 54 consecutively enrolled Japanese patients with rheumatoid arthritis (RA) and lymphoproliferative disease (LPD) relevant clinicopathological characteristics, in particular paying attention to treatment with methotrexate (MTX). Between the 28 patients treated with MTX (MTX-treated group) and the 26 who were not (non-MTX group), there was no difference in age, interval between onset of RA and LPD, and lymphoma stage. Immunohistochemical analysis showed that in the MTX-treated group, 15 (53 {\%}) patients had mature B-cell LPD, eight (29 {\%}) mature T/NK-cell LPD, and five (18 {\%}) had Hodgkin lymphoma. In the non-MTX group, 22 (84 {\%}) had mature B-cell LPD, 2 (8 {\%}) had mature T/NK-cell LPD, and 2 (8 {\%}) had Hodgkin lymphoma. The frequency of mature T/NK-cell LPD was significantly higher in the MTX-treated group (p < 0.05). Of the eight patients in the MTX-treated group with mature T/NK-cell LPD, two had large granular lymphocytic leukemia and the other six had a variety of different histological types with frequent CD8 but not CD56 expression. Epstein-Barr virus (EBV) infection was significantly higher in the MTX-treated group (p < 0.05); evidence of latent type II EBV infection was found in four of the eight patients with mature T/NK-cell LPD. Withdrawal of MTX led to complete remission in seven patients with mature T/NK-cell LPD irrespective of EBV infection. Our findings highlight that mature T/NK-cell LPD is a frequent complication in RA patients treated with MTX. EBV infection may play a role in the pathogenesis of T/NK-cell LPD, as well as B-cell LPD and Hodgkin lymphoma in MTX-treated RA patients.",
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AU - Kondo, Seiji

AU - Tanimoto, Kazuki

AU - Yamada, Kozue

AU - Yoshimoto, Goichi

AU - Suematsu, Eiichi

AU - Fujisaki, Tomoaki

AU - Oshiro, Yumi

AU - Tamura, Kazuo

AU - Takeshita, Morishige

AU - Okamura, Seiichi

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AB - We retrospectively analyzed in 54 consecutively enrolled Japanese patients with rheumatoid arthritis (RA) and lymphoproliferative disease (LPD) relevant clinicopathological characteristics, in particular paying attention to treatment with methotrexate (MTX). Between the 28 patients treated with MTX (MTX-treated group) and the 26 who were not (non-MTX group), there was no difference in age, interval between onset of RA and LPD, and lymphoma stage. Immunohistochemical analysis showed that in the MTX-treated group, 15 (53 %) patients had mature B-cell LPD, eight (29 %) mature T/NK-cell LPD, and five (18 %) had Hodgkin lymphoma. In the non-MTX group, 22 (84 %) had mature B-cell LPD, 2 (8 %) had mature T/NK-cell LPD, and 2 (8 %) had Hodgkin lymphoma. The frequency of mature T/NK-cell LPD was significantly higher in the MTX-treated group (p < 0.05). Of the eight patients in the MTX-treated group with mature T/NK-cell LPD, two had large granular lymphocytic leukemia and the other six had a variety of different histological types with frequent CD8 but not CD56 expression. Epstein-Barr virus (EBV) infection was significantly higher in the MTX-treated group (p < 0.05); evidence of latent type II EBV infection was found in four of the eight patients with mature T/NK-cell LPD. Withdrawal of MTX led to complete remission in seven patients with mature T/NK-cell LPD irrespective of EBV infection. Our findings highlight that mature T/NK-cell LPD is a frequent complication in RA patients treated with MTX. EBV infection may play a role in the pathogenesis of T/NK-cell LPD, as well as B-cell LPD and Hodgkin lymphoma in MTX-treated RA patients.

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