The Prevalence of Antibodies to an Epstein-Barr Virus-Induced Polypeptide (Ebna-2) in the Sera of Rheumatoid Arthritic Families

Hazelton, R. A.; Sculley, T. B.; Pope, J. H.

doi:10.1093/rheumatology/26.3.193

Cited by 11 publications

(8 citation statements)

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“…There have been many reports of high levels of EBV antibodies in RA patients (5)(6)(7)(8)(9)(10)(11). Our findings are consistent with those reports, and suggest that active EBV infection does exist in RA patients.…”

Section: Discussionsupporting

confidence: 92%

“…RA patients have a higher frequency and/or higher levels of serum antibodies against viral capsid antigen (VCA), early antigen (EA), and EBNA than normal individuals (5)(6)(7)(8)(9)(10)(11). It has been reported that the number of circulating B lymphocytes infected with EBV is increased in RA patients (12) and that EBV-specific T cell immunity is decreased (13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

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

Takeda

Mizugaki

Matsubara

et al. 2000

Arthritis & Rheumatism

102

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

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

Takeda

Mizugaki

Matsubara

et al. 2000

Arthritis & Rheumatism

102

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“…Furthermore, our results show that elevated ELISA OD 450 readings of IgG antibodies to the EBNA-2(N) are associated with SLE, RA or SSc and with secondary SS. These results have extended early reports that described a high incidence of anti-EBNA-2 antibodies in rheumatoid sera [51].…”

Section: Discussionsupporting

confidence: 88%

“…The more frequent presence of antibodies to EBNA-2 in sera from RA patients than in healthy control sera [50,51] has been documented, but the characteristics and significance of the EBNA-2 antibodies are unknown. The elevated levels of EBNA-2 IgG may not be a cause, but a result, of its antigenic cross-reactivity with cellular or other proteins of infectious agents.…”

Section: Discussionmentioning

confidence: 99%

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

Yamazaki

Kitamura

Kusano

et al. 2005

Clinical and Experimental Immunology

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SummaryAssociations of Epstein-Barr virus (EBV) and autoimmune diseases have been hypothesized. We have analysed IgG antibodies to EBV nuclear antigen (EBNA)-2 in sera from Japanese patients with autoimmune systemic connective tissue diseases (CTD), exemplified by systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), systemic sclerosis (SSc) and secondary SS (classical CTDs complicated with SS). An enzyme-linked immunosorbent assay (ELISA) which uses glutathione-Stransferase polypeptides fused to EBV nuclear antigen (EBNA)-2 and EBNA-1 was developed. Ratios of IgG antibody reactivity to whole IgG concentrations of sera were calculated to normalize EBNA-2 and EBNA-1 antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA optical density OD 450 readings of IgG antibodies to both the amino-terminal aa 1-116 of EBNA-2 and carboxyl-terminal aa 451-641 of EBNA-1 were elevated significantly in patients with SLE, primary SS, RA, SSc and secondary SS when compared to EBNA-1. The OD readings were divided by serum IgG concentrations to normalize for the hypergammaglobulinaemia. The specific levels of IgG antibodies to the amino-terminal region of EBNA-2 were elevated in patients with SLE, primary SS or RA, as well as those with secondary SS complicated with SLE or RA. The EBNA-2 amino-terminal region contains a polyproline tract and a proline-rich sequence and has considerable amino acid sequence homology with many cellular proline-rich proteins . High ratios of EBNA-2 aa 1-116 to EBNA-1 aa 451-641 IgG antibody levels which probably suggest reactivation of EBV latent infection were associated significantly with pulmonary involvement in SS patients. These results are consistent with the hypothesis that the sequence similarity between the amino-terminal region of EBNA-2 and proline-rich cellular proteins is associated with pathogenesis in a subpopulation of CTD patients, possibly by the molecular mimicry-epitope shift mechanism.

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“…6). A similar heterogeneity in molecular weight has been reported previously for EBNA-2 [23,24]. In contrast, anti-MC antibodies reacted with the 70-75 kDa polypeptides present exclusively in the immunoprecipitates of anti-VCP2 antibodies (Fig.…”

Section: Anti-vcp2 Antibodies Immunoprecipitate Citrullinated Ebna-2supporting

confidence: 87%

Antibodies to a new viral citrullinated peptide, VCP2: fine specificity and correlation with anti-cyclic citrullinated peptide (CCP) and anti-VCP1 antibodies

Pratesi

Tommasi

Anzilotti

et al. 2011

Clinical and Experimental Immunology

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SummaryAnti-citrullinated protein/peptide antibodies (ACPA) are a hallmark of rheumatoid arthritis (RA) and can be measured using different citrullinated substrates. In this paper we describe a new viral citrullinated peptide -VCP2 -derived from the Epstein-Barr virus-encoded protein EBNA-2 and analyse its potential as substrate for ACPA detection. Analysing sera from 100 RA patients and 306 controls, anti-VCP2 immunoglobulin (Ig)G were found in 66% of RA sera, IgM in 46% and IgA in 39%, compared with less than 3% of control sera. Anti-VCP2 IgG was associated with erosive arthritis, the presence of rheumatoid factor and anti-VCP1 and anti-cyclic citrullinated peptide (CCP) antibodies. Anti-VCP2 antibodies were detected in 1% and anti-VCP1 antibodies in 4% of CCP-negative RA sera; conversely, 3% of the VCPnegative sera were CCP-positive. Taken together, these data suggest that VCP2 could offer a valuable tool for ACPA detection. Inhibition assays showed that two non-overlapping epitopes -a citrulline-glycine stretch shared between VCP1 and VCP2 and the N-terminal portion of the VCP2 sequence -were targeted by anti-VCP2 antibodies. Moreover, in some RA sera that tested positive in CCP and VCP2 assays, preincubation with VCP2 inhibited binding to CCP, whereas in other sera the binding was unaffected. Thus, the reactivity with more than one ACPA substrate might be due in some RA patients to antibody populations with different specificities, and in others to crossreactive antibody populations. Finally, affinity-purified anti-VCP2 antibodies immunoprecipitated deiminated Epstein-Barr virus nuclear antigen (EBNA-2) from an EBNA-2-transfected cell line, suggesting that viral sequences may be involved in the generation of the ACPA response.

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The Prevalence of Antibodies to an Epstein-Barr Virus-Induced Polypeptide (Ebna-2) in the Sera of Rheumatoid Arthritic Families

Cited by 11 publications

References 0 publications

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

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

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

Antibodies to a new viral citrullinated peptide, VCP2: fine specificity and correlation with anti-cyclic citrullinated peptide (CCP) and anti-VCP1 antibodies

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