Altered immune response to glycine‐rich sequences of epstein‐barr nuclear antigen‐1 in patients with rheumatoid arthritis and systemic lupus erythematosus

Petersen, J.; Rhodes, Gary; Roudier, Jean; Vaughan, John H.

doi:10.1002/art.1780330711

Cited by 40 publications

(47 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly, in most earlier analyses of sera from RA patients EBNA-1 proteins containing either the Gly/Ala repeating region (aa 90-328), a major cross-reactive epitope region [53][54][55], or peptides derived from the Gly/Ala repeat sequence were used as antigen [23,56]. Our data show the statistical association of OD 450 readings of EBNA-1(C) IgG antibody with sera from primary SS patients (median = 0·459, P < 0·0007) but not RA patients, when compared to healthy controls (median = 0·369).…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…We assumed that the meaning of EA IgG was the same as in the normal population, that is to say the transient hallmarks of reactivation of latent virus. We reasoned that clinical/biochemical ‘footprints’ of EBV reactivation could be looked for among the signs of activity of the disease, EBV being recognized as a potent natural B-cell activator [45, 46, 47, 48]. …”

Section: Discussionmentioning

confidence: 99%

Correlation between Cytomegalovirus Infection and Raynaud’s Phenomenon in Lupus nephritis

Stratta

Canavese²,

Ciccone³

et al. 1999

Nephron

View full text Add to dashboard Cite

Relationships between viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) are still elusive. Recent reports demonstrated the association of some viral infections with peculiar clinical events in the general population, such as cytomegalovirus (CMV) with arterial damage and Parvovirus B19 (PV-B19) with hematologic abnormalities. We planned to look for this kind of viral imprinting in SLE, hypothesizing that traces of specific features of some viral infections might be found in some subsets of seropositive SLE patients. In 60 SLE patients recruited at our nephrologic center, serology for CMV, PV-B19, Epstein-Barr virus viral capsid antigen (EBV-VCA), Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr virus early antigen (EBV-EA) was performed. χ² and ANOVA were employed to compare the frequency and titers of antiviral antibodies in SLE patients with groups of transplant, hemodialysis and blood donor subjects. χ², Fisher’s test, Bonferroni and Scheffe’s test were employed to compare the different biochemical/clinical features between seropositive and seronegative SLE patients. Univariate and multivariate analysis (logistic regression models) were employed to evaluate the odds ratio (OR) of different risk factors for vascular events (including Raynaud’s phenomenon, deep venous thrombosis) and hematologic abnormalities (including severe anemia, leukopenia and thrombocytopenia). Anti-CMV (82%), anti-PV-B19 (60%), anti-EBV-VCA (92%) and EBV-EA (45%) IgG antibodies were frequent in SLE, with higher prevalence in comparison with the blood donor group and higher titers in comparison with transplant and hemodialysis groups. CMV seropositivity was a highly significant risk factor for Raynaud’s phenomenon (OR +α in univariate and multivariate analysis = 13.51 using a correction of 0.5 in case of a zero event), but not for venous vascular events (OR = 1.31). An increased though not significant risk factor was found for antiphospholipid antibodies (OR = 2.71, p = 0.19), while the presence of nephrotic syndrome during the follow-up was a significant protective factor (OR = 0.15, p = 0.035). There was no significantly increased OR for PV-B19 seropositivity in cases with severe anemia (OR = 2.09, p = 0.29). No significant associations were found with the status of EBV reactivation. In conclusion, our results support the hypothesis that viral infection may imprint the course of SLE leading to specific clinical subsets (i.e. CMV and ‘vascular’ SLE, with more frequent Raynaud’s phenomenon and a less frequent typical histological renal picture responsible for nephrotic syndrome). Further prospective studies are justified to validate these correlations, mainly dealing with associations between acute viral infections and vascular events, thus eventually leading to a better understanding of mutual relationships between viruses and SLE.

show abstract

“…EBNA-1 contains a large glycinearginine (GR) repeat that is homologous with a region on the C-terminal end of Sm D1, a lupus-associated autoantigen and component of the spliceosome [5,6]. Approximately 30% of tested sera from lupus patients bound to Sm-derived peptides containing the GR region, while sera from patients with rheumatoid arthritis, systemic sclerosis, or Sjö gren's syndrome did not.…”

Section: Spliceosomal Sm Systemmentioning

confidence: 99%

“…In the case of systemic lupus the data are consistent with at least three scenarios of autoimmunity being generated from the heteroimmune response against EBNA-1: PPPGRRP of EBNA-1 cross-reacting with PPPGMRPP of Sm B/B 0 [4], amino acids (aa) 35 -58 of EBNA-1(GPAGPRGGGRGRGRGRGR-GHNDGG) and aa 95 -119 of Sm D1 (RRPGGR-GRGRGRGRGRGRGRGRGA) [5], and aa 58 -72 (GGSGSGPRHRDGVRR) of EBNA-1 cross-reacting with aa 169 -180 (TKYKQRNSWSHK) of 60 kDa Ro [6].…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus

et al. 2006

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE or lupus) is a complex disease with a multifactoral etiology, with genetic, hormonal, and environmental influences. Molecular mimicry as a result of viral infection may contribute to the development of lupus. The pattern of autoantibody development in lupus is consistent with initiation through molecular mimicry, as the initial autoantigenic epitopes that have been observed are limited and cross-reactive with viral proteins. Autoantibody specificity may then later diversify to other autoantigens through B-cell epitope spreading. Epstein-Barr virus (EBV) is an excellent candidate to be involved in molecular mimicry in lupus. EBV infection has been associated with lupus through serological and DNA studies. Infection with EBV results in the production of the viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1), antibodies against which cross-react with lupus-associated autoantigens, including Ro, Sm B/B', and Sm D1, in lupus patients. The immune response against EBV, and EBNA-1 in particular, differs among lupus patients and healthy controls, with controls maintaining a limited humoral response and failing to produce long-standing cross-reactive antibodies. We hypothesize that the humoral immune response to EBNA-1 in susceptible individuals leads to the generation of cross-reactive antibodies. Through the process of epitope spreading, these cross-reactive antibodies target additional, non-cross reactive autoepitopes, spread to additional autoantigens, and become pathogenic, leading eventually to clinical lupus. This paper reviews some of the current literature supporting roles for EBV exposure and epitope spreading in SLE.

show abstract

Altered immune response to glycine‐rich sequences of epstein‐barr nuclear antigen‐1 in patients with rheumatoid arthritis and systemic lupus erythematosus

Cited by 40 publications

References 19 publications

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

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

Correlation between Cytomegalovirus Infection and Raynaud’s Phenomenon in Lupus nephritis

Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus

Contact Info

Product

Resources

About