How compelling are the data for Epstein–Barr virus being a trigger for systemic lupus and other autoimmune diseases?

Draborg, Anette Holck; Izarzugaza, José M. G.

doi:10.1097/bor.0000000000000289

Cited by 61 publications

(45 citation statements)

References 48 publications

(25 reference statements)

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“…It has been reported that some chronic viral infections might be the trigger or at least are associated with, of autoimmunity, in particular due to cross-reactivity, as has been observed in several tropical viral infections such as Chikungunya (48), Epstein-Barr (49), and Zika (50), which have been associated with acute arthritis of unknown origin and have been poorly characterized (51, 52). In this regard, several genes of the IFN signature such as MXA and MXB have been associated with protection against viral infection (53, 54).…”

Section: Discussionmentioning

confidence: 99%

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

et al. 2017

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BackgroundRheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual’s life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies.MethodsSamples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA−), and healthy controls were recruited at “Unidad de Artritis y Rheumatismo” (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen.ResultsSignificant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA− in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05).ConclusionOur data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

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Section: Discussionmentioning

confidence: 99%

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

et al. 2017

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“…The investigation of patients with EBV-infected tumors has provided a reasonable degree of proof that EBV was present before neoplastic transformation, which highlights the need to further elucidate how much EBV contributes to tumorigenesis [4]. EBV is also associated with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and multiple sclerosis [19][20][21]. Furthermore, the virus is associated with a wide variety of benign and neoplastic diseases including posttransplant lymphoproliferative disorder (PTLD) and NPC (which are almost exclusively EBV-related), Hodgkin's and non-Hodgkin's lymphomas, and gastric carcinoma ( Table 2).…”

Section: Ebv-associated Diseasesmentioning

confidence: 99%

“…Interestingly, viral load relates to disease severity in lymphoproliferative disease and EBV-associated malignancies, making it a useful prognostic marker [44]. Nevertheless, the improper storage of whole blood can cause either a false-positive finding if EBV-DNA leaves the intracellular compartment or a false-negative finding if the nucleases degrade plasma EBV-DNA [21,29,69].…”

Section: Molecular Assaysmentioning

confidence: 99%

Recent Advances in Diagnostic Approaches for Epstein–Barr Virus

et al. 2020

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my (M.A.H.A.); irekeola@student.usm.my (A.A.I.); hanimkk@usm.my (R.H.S.)Abstract: Epstein-Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV. Methods such as the heterophile antibody test, immunofluorescence assays, enzyme immunoassays, Western blot, and polymerase chain reaction (PCR) are also employed in the detection of EBV in different types of samples. The determination of EBV viral load using PCR, however, is gaining more prominence in the diagnosis of EBV-associated diseases. Given the challenge of false positive/negative results that are sometimes experienced during the detection of EBV, variability in results from different laboratories, and the impact of factors such as sample type and the immunological status of patients from whom samples are collected, the need to critically examine these present methods is invaluable. This review thus presents current advances in the detection of EBV, detailing the advantages and disadvantages of the various techniques. In addition, fundamental virological concepts are highlighted to enhance the greater understanding, the proper application, and the interpretation of EBV tests.Pathogens 2020, 9, 226 2 of 17 EBV can infect a wide range of cells and tissues including T and B lymphocytes, nasopharynx and oropharynx squamous epithelial cells, salivary and stomach glands, thyroid glandular epithelial cells, smooth muscle, and follicular dendritic cells [4]. However, EBV primarily infects and replicates in the stratified squamous epithelium of the oropharynx, followed by a latent infection of B lymphocytes [4]. It has been suggested that the EBV infection of B lymphocytes occurs in the oropharyngeal lymphoid organs [2]. In normal carriers, the virus persists in circulating memory B cells and initiates the production of immunoglobulins [1,2]. Following EBV's infection of B cells, a specific set of latency-related genes and transcripts are expressed, and the virus could remain dormant in resting memory B cells, from which it intermittently reactivates at any mucosal site where B cells are present (Table 1) [4,5]. The reactivation of EBV poses a great and difficult challenge to infected hosts [3]. In healthy adults, it is estimated that for every million B cells in circulation, approximately 1 to 50 are infected with EBV, with the number of latently-infected cells in each individual remaining stable for several years [6]. Therefore, EBV coexists with most human hosts without obvious outcomes. However, in some people, the virus is associated with the develo...

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“…Studies in this sense have already been carried out within the limited scope of work on the origin recognition complex and demonstrating how EBV uses its own genes to initiate its replicative machinery [7]. Moreover, at the clinical level, the causal role played by EBV has been demonstrated, in connection with other viral factors and immune disorders involved in the etiopathogenesis of systemic lupus erythematosus [8].…”

Section: Org/about/ What-is-systems-biologymentioning

confidence: 99%

Epstein - Barr virus Reactivation Associated with an Increased Thymidine Kinase and Normalized by an Immuno Modulatory Nano-Therapy: Three Case Reports

2018

JCEI

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Epstein-Barr Virus (EBV), a common human herpes virus known to infect most of the world population, has been mentioned in the context of many diverse human pathologies while its participation during its latency phase is more and more often demonstrated in a growing number of chronic malignancies.The biological diagnosis of the virus activity is carried out using serological parameters on the one hand, and the measurement of the viral load on the other hand. Thymidine kinase (TK) is a key enzyme in the regulation of the intranuclear thymidine pool during cell cycle progression. The rise in its plasma level therefore systematically reveals an uncontrolled cellular proliferation evoking, of course, at first a neoplastic process. Nevertheless, EBV being a DNA virus, its reactivation or even a persistent primary infection are also likely to cause an increase in the blood level of TK.Using three examples, we will show that the neutralization of EBV by an immunomodulatory nano-therapy called Bio Immune (G)ene Medicine (BI(G)MED), is accompanied by a normalization of plasma levels of TK, thus underlining the close link between the virus and this marker of cell proliferation.

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How compelling are the data for Epstein–Barr virus being a trigger for systemic lupus and other autoimmune diseases?

Cited by 61 publications

References 48 publications

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production

Recent Advances in Diagnostic Approaches for Epstein–Barr Virus

Epstein - Barr virus Reactivation Associated with an Increased Thymidine Kinase and Normalized by an Immuno Modulatory Nano-Therapy: Three Case Reports

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