Epstein–Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A antibodies in systemic lupus erythematosus patients

Draborg, Anette Holck; Jørgensen, Jan; Müller, Holger M.; Nielsen, Christoffer Tandrup; Jacobsen, Søren; Iversen, Line V.; Theander, Elke; Nielsen, Lars Peter; Houen, Gunnar; Duus, Karen

doi:10.3109/03009742.2012.665944

Cited by 42 publications

(51 citation statements)

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“…If the enhanced IgG response against EBNA-6 may be of diagnostic relevance in a subgroup of patients needs to be analysed in a longitudinal study. Cross-reactivity of EBV-specific IgG with human antigens due to antigenic mimicry is known to trigger pathogenic immune responses in SLE and MS [75–77]. We thus performed a sequence comparison of the EBNA-6 repeat region with human proteins and identified a 7 amino acids homologous sequence in the LPO protein, an enzyme producing oxidants and secreted by mammary, salivary and mucous glands of the bronchia.…”

Section: Discussionmentioning

confidence: 99%

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

et al. 2017

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BackgroundEpstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients.MethodsWe performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples.ResultsEBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins.ConclusionPatients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry.

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Section: Discussionmentioning

confidence: 99%

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

et al. 2017

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“…Furthermore, elevated titers of IgG antibodies to EA/D, EA/R, and BALF2 have been observed in about half of SLE patients compared to only 8–17% of healthy controls [60, 62, 63, 66, 67]. Additionally, high levels of IgA antibodies to EA/D have been found in 58% of SLE patients and not in healthy controls [68, 69]. These results could not be explained by immunosuppressive medication, indicating that the antibodies are not produced upon reactivation of EBV due to an iatrogenically suppressed immune system.…”

Section: Ebv In Sadsmentioning

confidence: 99%

Epstein-Barr Virus in Systemic Autoimmune Diseases

Draborg

Duus

Houen

2013

Clinical and Developmental Immunology

194

144

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Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

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“…EA(D)-IgG/EA(D)-IgA is an excellent marker for detecting active and reactivating EBV infection conditions (Glaser et al 2005;Kimura 2006;Draborg et al 2012). However, Zebra/Zta IgG responses are not limited to patients with acute chronic (malignant) infections, but are generally detectable in healthy EBV carriers, well beyond the acute phase.…”

Section: Molecular Details Of Anti-ebv Antibody Responses During and mentioning

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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Epstein–Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A antibodies in systemic lupus erythematosus patients

Cited by 42 publications

References 47 publications

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

Epstein-Barr Virus in Systemic Autoimmune Diseases

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

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