Lytic Epstein‐Barr virus infection in the synovial tissue of patients with rheumatoid arthritis

Takeda, Tsuyoshi; Mizugaki, Yuzo; Matsubara, L.; Imai, Shosuke; Koike, Takao; Takada, Kenzo

doi:10.1002/1529-0131(200006)43:6<1218::aid-anr4>3.0.co;2-2

Cited by 101 publications

(48 citation statements)

References 36 publications

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“…27 By analysis of BZLF1 in EBER1/2-positive cases in this study, however, only very few single BZLF1-positive cells in rare foci could be identified in three cases beside extensive expression of LMP1 in numerous cells suggesting, that lytic EBV-infection is a rare event.…”

Section: Discussioncontrasting

confidence: 58%

“…Synovial lining cells do not express the EBV receptor CD21. 27 Thus, as shown in human epithelial cells, EBV probably enters synovial cells via cellto-cell-contact with EBV-infected lymphocytes. 28 EBER1 and EBER2 are small nontranslated EBVencoded nuclear RNA, which are transcribed in very high copy number (10 7 copies per cell) in as well latent as lytic cycle of EBV-infection.…”

Section: Discussionmentioning

confidence: 86%

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Latent Epstein–Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization

et al. 2004

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 86%

Latent Epstein–Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization

et al. 2004

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“…Another study detected EBV infection in synovial tissue from patients with RA but not in patients with osteoarthritis (42,43), although other investigators failed to confirm these findings (44). Although it is not yet clear whether this viral overload is specific for EBV, it certainly could provide a chronic antigenic stimulus leading to the processing of viral proteins and the presentation of EBV-derived peptides.…”

Section: Discussionmentioning

confidence: 98%

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

117

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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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“…4 These results are particularly interesting, because EBV is frequently found in the synovium of RA patients 28 and these patients could have impaired immunologic control of EBV. 29 As compared to populations with no immunodeficiency, an association with EBV could be slightly more frequent in our patients: EBV was detected in 5 of 7 HD patients, in 2 of 12 with diffuse large B-cell NHL, and in 1 with LGL T-cell NHL.…”

Section: Discussionmentioning

confidence: 99%

Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France

Mariette

Cazals–Hatem²,

Warszawki³

et al. 2002

Blood

385

229

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-1.7). The estimated annual incidence rate of HD among men and women was, respectively, 27.8.10 ؊5 (0-70.1) and 2.8.10 ؊5 (0-9.6). The incidence of HD was significantly increased compared with the French incidence, with an SMR adjusted for age and sex of 7.4 (3.0-15.3; P < .001). Thus, this 3-year prospective study indicated that, whereas the risk of NHL was not significantly increased in RA patients treated with MTX, the incidence of HD appeared to be higher in these patients compared to the French population.

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Lytic Epstein‐Barr virus infection in the synovial tissue of patients with rheumatoid arthritis

Abstract: EBV was frequently detected in the synovial tissue of RA patients. The infected cells were both lymphocytes and synovial cells, and expressed EBV proteins associated with virus replication. These findings suggest that EBV may play a role in the pathogenesis of RA.

Cited by 101 publications

References 36 publications

Latent Epstein–Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization

Latent Epstein–Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization

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

Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France

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