Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis.

Tosato, Giovanna; Steinberg, Alfred D.; Yarchoan, Robert; Heilman, Carole A.; Pike, Sandra E.; Seau, V De; Blaese, R. Michael

doi:10.1172/jci111388

Cited by 181 publications

(86 citation statements)

References 30 publications

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“…It has been convincingly demonstrated that peripheral T lymphocytes from patients with RA are not efficient in the killing of autologous EBV-infected lymphoblastoid B lines (39), and that the frequency of EBV-infected peripheral B lymphocytes is higher in patients with RA than in controls (40).…”

Section: Discussionmentioning

confidence: 99%

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

Pratesi

Tommasi

Anzilotti

et al. 2006

Arthritis & Rheumatism

120

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Objective. To test the hypothesis that deimination of viral sequences containing Arg-Gly repeats could generate epitopes recognized by anti-citrullinated protein antibodies (ACPAs) that are present in rheumatoid arthritis (RA) sera.Methods. Multiple antigen peptides derived from Epstein-Barr virus (EBV)-encoded Epstein-Barr nuclear antigen 1 (EBNA-1) were synthesized, substituting the arginines with citrulline, and were used to screen RA sera. Anti-cyclic citrullinated peptide antibodies were purified by affinity chromatography and tested on a panel of in vitro deiminated proteins. Their ability to bind in vivo deiminated proteins was evaluated by immunoprecipitation, using EBV-infected cell lines.Results. Antibodies specific for a peptide corresponding to the EBNA-1 35-58 sequence containing citrulline in place of arginine (viral citrullinated peptide [VCP]) were detected in 50% of RA sera and in <5% of normal and disease control sera. In addition, affinitypurified anti-VCP antibodies from RA sera reacted with filaggrin-derived citrullinated peptides, with deiminated fibrinogen, and with deiminated recombinant EBNA-1. Moreover, anti-VCP antibodies immunoprecipitated, from the lysate of calcium ionophore-stimulated lymphoblastoid cell lines, an 80-kd band that was reactive with a monoclonal anti-EBNA-1 antibody and with anti-modified citrulline antibodies.Conclusion. These data indicate that ACPAs react with a viral deiminated protein and suggest that EBV infection may play a role in the induction of these RA-specific antibodies.

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Section: Discussionmentioning

confidence: 99%

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

Pratesi

Tommasi

Anzilotti

et al. 2006

Arthritis & Rheumatism

120

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“…I3l ,211,248 Expanded numbers of EBV-containing cells have been described in patients with chronic lymphocytic leukemias and rheumatoid arthritis. 258 The virus is not thought to be causative in these two disorders, and the significance of these associations is not known. Garden variety non-Hodgkin's B-celllymphomas do not normallv exhibit evidence of EBV involvement.…”

Section: Epstein-barr Virus Biology and Infectionmentioning

confidence: 99%

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Nalesnik

Makowka

Starzl

1988

Current Problems in Surgery

249

111

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“…T lymphocytes from their peripheral blood are less efficient at controlling the outgrowth of EBV-infected B cells (2). Patients with RA have more EBV-infected B cells than normal individuals (3). Disease activity is associated with lower T cell responses to the EBV replication protein gp110 (4).…”

Section: Introductionmentioning

confidence: 99%

Long‐term treatment with methotrexate or tumor necrosis factor α inhibitors does not increase epstein‐barr virus load in patients with rheumatoid arthritis

Balandraud¹,

Guis²,

Meynard³

et al. 2007

Arthritis & Rheumatism

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Objective. We previously demonstrated that patients with rheumatoid arthritis (RA) have a 10-fold systemic EpsteinBarr virus (EBV) overload, very similar to that observed in healthy organ transplant recipients. Our objective was to monitor EBV load over time in patients with RA receiving methotrexate, infliximab, or etanercept to detect possible immunosuppression-associated EBV dysregulation, as described in posttransplant lymphoproliferative disease. Methods. The EBV load in the peripheral blood mononuclear cells (PBMCs) from 19 patients receiving methotrexate, 68 patients receiving infliximab, and 48 patients receiving etanercept was monitored for durations ranging from 6 months to 5 years using a real-time polymerase chain reaction assay previously developed for that purpose. The effect of treatment duration on EBV load and the link between the Disease Activity Score in 28 joints and EBV load were analyzed by generalized estimating equations. Results. Methotrexate tended to decrease EBV load over time, but this did not reach significance. Tumor necrosis factor ␣ (TNF␣) inhibitors did not significantly modify EBV load over time. Finally, high disease activity was significantly associated with high EBV load. Conclusion. Long-term usage of methotrexate or TNF␣ inhibitors in patients with RA does not significantly influence EBV load in PBMCs.

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Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis.

Cited by 181 publications

References 30 publications

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Long‐term treatment with methotrexate or tumor necrosis factor α inhibitors does not increase epstein‐barr virus load in patients with rheumatoid arthritis

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