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

Kitamura, Noboru; Sugiyama, K.; Nagasawa, Y.; Hamaguchi, Marina; Kobayashi, Hitomi; Takei, Masami

doi:10.55563/clinexprheumatol/lgfbtq

Cited by 4 publications

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“…Strategies for the first use of methotrexate (MTX) should be considered based on treatment recommendations for RA. However, since EBV-DNA was positive in this case, there was a strong concern about other iatrogenic immunodeficiency-associated lymphoproliferative disorders ( 20 , 21 ) due to the use of MTX. Another concern was the exacerbation of EBV reactivation associated with TCZ use.…”

Section: Discussionmentioning

confidence: 84%

Successful Treatment of SARS-CoV-2 Vaccination-related Activation of Rheumatoid Arthritis with Positive Findings for Epstein-Barr Virus

et al. 2022

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We herein report a 60-year-old woman who experienced severe flare of rheumatoid arthritis (RA) and Epstein-Barr virus (EBV) positivity following administration of the messenger ribonucleic acid (mRNA)-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Since 40 years old, she had been in long-term remission of anti-citrullinated protein antibody-positive RA. Ten days after SARS-CoV-2 vaccination, she presented with a high fever and polyarthritis, active synovitis on joint ultrasound, a clinical disease activity index of 35, and positivity for anti-early antigen, diffuse type and restricted type (EA DR) IgG and EBV deoxyribonucleic acid (EBV-DNA). Tocilizumab was introduced to treat RA. The RA disease activity disappeared, and anti-EA DR IgG and EBV-DNA became negative.

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Section: Discussionmentioning

confidence: 84%

Successful Treatment of SARS-CoV-2 Vaccination-related Activation of Rheumatoid Arthritis with Positive Findings for Epstein-Barr Virus

et al. 2022

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“…Ejima-Yamada et al [ 30 ] reported that spontaneous regression of LPDs by withdrawal of MTX and biologic drugs was frequently found in 15 of 21 RA patients with OIIA EBV+ B-LPDs (71%), as opposed to none of 17 OIIA EBV− B-LPDs (0%) ( p < 0.01). Another recent study demonstrated that high EBV real-time PCR value, improvement of lymphocyte counts in the peripheral blood, and patients with EBER+ cells in the involved tissues were significantly associated with the spontaneous regression of LPDs by withdrawal of MTX and biologic drugs in 34 RA patients with LPDs ( p = 0.003, p = 0.036, and p = 0.032, respectively) [ 31 ]. These findings highly suggest that tumour microenvironments and lymphomagenesis caused by EBV in RA patients occurred in the immunosuppressive states caused by MTX, THF inhibitors, and other biologic drugs.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders

et al. 2022

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Background Other iatrogenic immunodeficiency-associated (OIIA) T- and natural killer (NK)-cell lymphoproliferative disorders (TNK-LPDs) are rare in patients with rheumatoid arthritis (RA). Methods We investigated the clinicopathological characteristics, Epstein–Barr virus (EBV) infection, genetic findings, therapeutic response, and prognostic factors in 21 RA patients with OIIA TNK-LPDs and compared these with those of 39 with OIIA B-cell LPDs (B-LPDs) and 22 with non-OIIA B-LPDs. Results Immunohistologically, 11 patients (52%) showed CD4+ T-LPDs, and 7 had a T follicular helper (TFH) phenotype. The other nine patients (43%) showed CD8+ T-LPDs, and the remaining one (5%) had features of CD3+ CD4− CD8− nasal type TNK-cell lymphoma. CD30+, p53+, and CMYC+ atypical lymphocytes were identified in seven (33%), eight (38%), and five (24%) patients, respectively. In situ hybridisation detected EBV-encoded RNA (EBER) + large atypical lymphocytes in five patients (24%). Nine of 17 patients (53%) showed clonal peaks of TCRγ by polymerase chain reaction. Withdrawal of MTX and biologic drugs was effective in 12 patients (57%), and 8 (38%) received chemotherapies. Two patients with TFH+ or EBV+ CD4+ CD30+ large cell peripheral T-cell lymphoma, one with CD8+ systemic anaplastic large cell lymphoma, and two with systemic EBV+ CD8+ T-cell lymphoma of childhood showed a lethal progressive clinical course within 13 months. Moreover, > 500 U/L LDH, large atypical lymphocytes, expression of CD30, p53, and CMYC, and EBER+ atypical lymphocytes were significantly poor prognostic factors for overall survival (p < 0.05). Median interval from RA onset to OIIA TNK-LPDs was 72 months, which was shorter than 166 months in OIIA B-LPDs (p = 0.003). EBV+ atypical and reactive lymphocytes were frequently found in 15 patients with OIIA TNK-LPDs (71%), in 27 with OIIA B-LPDs (69%), and only in 3 with non-OIIA B-LPDs (14%). Conclusions OIIA TNK-LPDs occurred in early phase of RA, compared with OIIA B-LPDs, and occasionally showed a lethal progressive clinical course. Detection of OIIA TNK-LPD patients with poor prognostic factors is necessary. EBV infection in immunosuppressed patients due to persistent RA, MTX, and biologic drugs may play a role in forming the tumour microenvironment and lymphomagenesis of TNK-LPDs.

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“…Of the IDD-LPDs, the most common type of lymphoma encountered is diffuse large B-cell lymphoma (DLBCL-IDD), accounting for 35-60% of cases, followed by classic Hodgkin lymphoma (CHL-IDD) at 12-28% [12,13,16]. From the clinical point of view, IDD-LPDs exhibit one unique characteristic, which is the spontaneous resolution that occurs in 25-81.8% of patients after MTX withdrawal [16][17][18][19][20][21][22][23]. While DLBCL-IDD typically exhibits spontaneous resolution without recurrence, most cases of CHL-IDD are associated with relapses that necessitate chemotherapy [5,24,25].…”

Section: Introductionmentioning

confidence: 99%

Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation

Ohsawa,

Momose,

Nishikori

et al. 2024

Cancers

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A subset of patients with rheumatoid arthritis receiving methotrexate develop immune deficiencies and dysregulation-associated lymphoproliferative disorders. Patients with these disorders often exhibit spontaneous regression after MTX withdrawal; however, chemotherapeutic intervention is frequently required in patients with classic Hodgkin lymphoma arising in immune deficiency/dysregulation. In this study, we examined PD-L1 expression levels and 9p24.1 copy number alterations in 27 patients with classic Hodgkin lymphoma arising from immune deficiency/dysregulation. All patients demonstrated PD-L1 protein expression and harbored 9p24.1 copy number alterations on the tumor cells. When comparing clinicopathological data and associations with 9p24.1 copy number features, the copy gain group showed a significantly higher incidence of extranodal lesions and clinical stages than the amplification group. Notably, all cases in the amplification group had latency type II, while 6/8 (75%) in the copy gain group had latency type II, and 2/8 (25%) had latency type I. Thus, a subset of the copy-gain group demonstrated more extensive extranodal lesions and higher clinical stages. This finding speculates the presence of a genetically distinct subgroup within the group of patients who develop immune deficiencies and dysregulation-associated lymphoproliferative disorders, which may explain certain characteristic features.

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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

Cited by 4 publications

References 0 publications

Successful Treatment of SARS-CoV-2 Vaccination-related Activation of Rheumatoid Arthritis with Positive Findings for Epstein-Barr Virus

Successful Treatment of SARS-CoV-2 Vaccination-related Activation of Rheumatoid Arthritis with Positive Findings for Epstein-Barr Virus

Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders

Copy Number Analysis of 9p24.1 in Classic Hodgkin Lymphoma Arising in Immune Deficiency/Dysregulation

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