Monitoring of Epstein–Barr virus load and killer T cells in patients with juvenile idiopathic arthritis treated with methotrexate or tocilizumab

Fujieda, Mikiya; Tsuruga, Kazushi; Sato, Tetsuya; Kikuchi, Hiroaki; Tamaki, Wataru; Imamura, Masayuki; Yamamoto, Masaki; Oishi, Taku; Tanaka, Hiroshi; Daibata, Masanori

doi:10.1080/14397595.2016.1177247

Cited by 7 publications

(8 citation statements)

References 26 publications

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“…Our study showed significant (p = 0.021) decrease of EBV load under Tocilizumab, as published by others [ 23 , 24 ]. In a recent cross-sectional case-control study, Erre GL et al studied EBV load by Real time PCR in one hundred thirty-five Sardinians (77 RA patients and 58 healthy donors, HDs).…”

Section: Discussionsupporting

confidence: 90%

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Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study

et al. 2017

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BackgroundEpstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas. Immunosuppressive drugs used to treat RA (conventional disease modifying drugs cDMARDs or biologics bDMARDs) could enhance the risk of developing LPD in RA patients. We have previously shown that long term treatment with Methotrexate and/or TNF alpha antagonists does not increase EBV load in RA. Our objective was to monitor the Epstein-Barr Virus load in RA patients treated with Abatacept (CTLA4 Ig), a T cell coactivation inhibitor, and Tocilizumab, an anti IL6 receptor antibody.MethodsEBV load in the peripheral blood mononuclear cells (PBMCs) of 55 patients under Abatacept (in 34% associated with Methotrexate) and 35 patients under Tocilizumab (in 37% associated with Methotrexate) was monitored for durations ranging from 6 months to 3 years by real time PCR. The influences of treatment duration and disease activity score 28 (DAS28) index on EBV load were analyzed.ResultsAbatacept did not significantly modify EBV load over time. Tocilizumab significantly diminished EBV load over time. No patient (of 90) developed EBV associated lymphoma.ConclusionLong term treatment with Abatacept or Tocilizumab does not increase EBV load in the PBMNCs of patients with RA.

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Section: Discussionsupporting

confidence: 90%

“…Mourgues et al monitored EBV load in 20 patients with RA treated by tocilizumab and found no increase [ 23 ]. Fujieda et al followed Epstein-Barr virus load for three years in peripheral blood lymphocytes patients with juvenile idiopathic arthritis treated with methotrexate and tocilizumab and found it to decrease [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study

et al. 2017

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“…Published studies to date have not revealed differences in the number of EBV copies in the PBMC of patients with JIA compared to controls [9][10][11][12]. In our study, we did not observe any differences in the occurrence of EBV viremia in the studied groups, so the connection with the prevalence of arthritis was not demonstrated.…”

Section: Discussioncontrasting

confidence: 81%

The Impact of Epstein-Barr Virus Infection on Juvenile Idiopathic Arthritis Activity and Patient’s Response to Treatment

Opoka-Winiarska

Grywalska

Sobiesiak

et al. 2020

JCM

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This study aimed to investigate the relationship between Epstein-Barr virus (EBV) infection and the onset of juvenile idiopathic arthritis (JIA), disease activity, and response to treatment. The study included 44 children with JIA, 23 children with different types of arthritis, and 44 controls. We measured EBV infection markers, including the EBV DNA load and the concentration of antibodies to viral antigens, at disease onset, before treatment. Six months after JIA diagnosis and the initiation of treatment patients with anti-viral capsid antigen IgG had a higher disease activity and worse response to treatment than patients without previous infection. After six months of treatment, the probability of disease inactivity in children without a history of EBV infection was almost 6.5 times greater than in a child with a history of infection. Furthermore, the probability of a better response after six months of treatment in a child with a history of EBV infection was more than five times smaller than in a child without infection. A past EBV infection can have a negative effect on achieving disease remission and may be associated with a worse response to treatment. Our results do not indicate the need for routine assessment of EBV infection markers in patients with JIA.

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“…Impairment due to EBV, as indicated by impaired T-cell response against EBV and increased EBV viral load after MTX administration, has been reported in patients with RA, 170 - 175 and several reports demonstrated the association between EBV viral road and disease activity in patients with juvenile idiopathic arthritis who developed MTX-LPD 176 . In contrast, several recent studies reported that the EBV viral load does not increase under the administration of ISDs such as MTX, TNFi, and ABT 177 - 179 …”

Section: Prediction Of Mtx-lpdmentioning

confidence: 99%

Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative disorders

Tokuhira¹,

Tamaru²,

Kizaki³

2019

JCEH

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Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD), a category of immunodeficiency-associated LPD according to the World Health Organization classification, is associated with immunosuppressive drugs (ISDs). Several factors, including autoimmune disease (AID) activity, Epstein-Barr virus (EBV) infection, ISD usage, and aging, influence the development of OIIA-LPD, resulting in complicated clinical courses and outcomes. Most OIIA-LPD develops in patients with rheumatoid arthritis using methotrexate (MTX-LPD). The management of MTX-LPD is based on the clinical course, i.e., with/without regression, with/without relapse/regrowth event (RRE), LPD subtype, and ISDs for AIDs after LPD development. There are three clinical courses after ISD withdrawal: regressive LPD without relapse/regrowth (R-G), regressive LPD with RRE (R/R-G), and persistent LPD (P-G). The majority of EBV+ diffuse large B-cell lymphomas are classified in R-G, whereas classic Hodgkin lymphoma is generally classified in R/R-G. Polymorphic LPD (P-LPD) in MTX-LPD develops with heterogeneous pathological features similar to monomorphic LPD. Chemotherapy for MTX-LPD is selected according to that for de novo LPD, although the strategy for aggressive P-LPD and non-specific LPD is not well established. The absolute lymphocyte count in the peripheral blood has been suggested as a candidate marker for MTX-LPD development and RRE. Several clinical issues, including correct diagnosis among overlapping clinicopathological features in MTX-LPD and clinical management of LPD by ISDs other than MTX, require further investigation.

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Monitoring of Epstein–Barr virus load and killer T cells in patients with juvenile idiopathic arthritis treated with methotrexate or tocilizumab

Abstract: Treatment with MTX and/or TCZ did not severely affect EBV load and prevent induction of EBV-CTLs in JIA patients.

Cited by 7 publications

References 26 publications

Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study

Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study

The Impact of Epstein-Barr Virus Infection on Juvenile Idiopathic Arthritis Activity and Patient’s Response to Treatment

Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative disorders

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