Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen.

Fox, Robert I.; Sportsman, Richard; Rhodes, Gary; Luka, János; Pearson, Gary R.; Vaughan, John H.

doi:10.1172/jci112469

Cited by 79 publications

(32 citation statements)

References 48 publications

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“…) indicate that CD5' B cells from patients with SLE are not increased in number and do not spontaneously proliferate in vitro, suggesting that different mechanisms are operative in SLE and RA. Although EBV has been suggested as a possible factor in the pathogenesis of RA (24,25), immunofluorescence and in situ DNA hybridization on the spontaneously proliferating CD5' cells has failed to show any evidence of EBV infection (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis.

Burastero

Casali

Wilder

et al. 1988

The Journal of Experimental Medicine

257

129

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In patients with rheumatoid arthritis (RA), circulating CD5+ B lymphocytes, but not CD5- B lymphocytes, are increased in number and size, exist in an activated state, spontaneously proliferate, and secrete Ig that binds to the Fc fragment of IgG. By constructing continuous mAb-secreting cell lines from CD5+ B lymphocytes, the properties and dissociation constants (Kd) of these antibodies were determined. Two types of rheumatoid factors (RFs) with discrete reactivities were produced. The first type is polyreactive and binds with relatively low affinity (Kd, 10(-5) mol/liter) to the Fc fragment of IgG. These antibodies are similar to those produced by CD5+ B cells from healthy subjects. The second type of RF is monoreactive and binds with higher affinity (Kd, 10(-7) mol/liter) to the Fc fragment of IgG. These latter autoantibodies are produced by CD5+ B cells of RA patients, but not healthy subjects. Long-term longitudinal studies are needed to determine the role of these two types of RFs in the pathogenesis of RA.

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Section: Discussionmentioning

confidence: 99%

Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis.

Burastero

Casali

Wilder

et al. 1988

The Journal of Experimental Medicine

257

129

View full text Add to dashboard Cite

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“…EBNA1 was shown to have a long glycine-alanine (Gly-Ala) repeat, which varied in size between different EBV genomes. In 1984, a synthetic Gly-Ala repeat peptide was identified as major antigenic domain of EBNA1, but later found to be cross-reactive with "self-proteins" and reactive with sera from acute CMV infection and some autoantibodies as well (Fox et al 1986;Rhodes et al 1990;Levine et al 1994). In 1985, Milman and colleagues at John's Hopkins, Baltimore, USA, defined that the C-terminal domain of EBNA1 formed a reliable, stable and highly reactive EBNA reagent suitable for serological studies .…”

Section: The Ebna Complexmentioning

confidence: 99%

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

Middeldorp

2015

Current Topics in Microbiology and Immunology

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Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

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“…EpsteinBarr virus (EBV) infection might be among the factors that are involved in both rheumatoid arthritis (RA) [17][18][19][20][21][22][23] and in Sjögren syndrome (SS) [24,25].…”

mentioning

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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Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen.

Abstract: A monoclonal antibody, selected for reactivity with the Epstein-

Cited by 79 publications

References 48 publications

Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis.

Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis.

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

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

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