High anti‐EBNA‐1 IgG levels are associated with early‐onset myasthenia gravis

Csuka, Dorottya; Bánáti, Miklós; Rózsa, Csilla; Füst, George; Illés, Zsolt

doi:10.1111/j.1468-1331.2011.03636.x

Cited by 30 publications

(31 citation statements)

References 18 publications

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“…Indeed, we found positivity for EBV latency and lytic markers in B cells and plasma cells of GCs and B cell lymphoid infiltrates present in MG thymuses, supporting the idea that EBV might be responsible for maintenance of the autoimmune response in MG thymus, possibly because of its ability to activate and immortalize B cells . In line with a contribution of EBV in MG was the observation that high serum levels of antibodies against the type 1 nuclear antigen of EBV (EBNA1) are more frequent in MG patients, especially those with early‐onset MG, compared with healthy controls …”

Section: Tlrs In Intrathymic Mg Pathogenesis: a Bridge Between Innatesupporting

confidence: 76%

“…31,35 In line with a contribution of EBV in MG was the observation that high serum levels of antibodies against the type 1 nuclear antigen of EBV (EBNA1) are more frequent in MG patients, especially those with early-onset MG, compared with healthy controls. 41 Our recent study also provided evidence of an altered expression of genes associated with infections (e.g., ETF1, NFKB2, PLK3, and PPP1R15A) and inflammation (e.g., ABCA1, FUS, and RELB) in peripheral blood mononuclear cells (PBMCs) of MG patients. 42 These results, along with literature data showing overexpression of some TLRs, including TLR3, TLR4, TLR8, and TLR9, in PBMCs of MG patients, 18 indicate that TLR-mediated innate immune mechanisms triggering or favoring the autoimmune process in MG thymus can perpetuate immune dysregulation and autoimmunity also in peripheral blood, and possibly in regional lymph nodes.…”

Section: Tlrs In Intrathymic Mg Pathogenesis: a Bridge Between Innatementioning

confidence: 74%

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Toll‐like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?

Cavalcante

Barzago

Baggi

et al. 2018

Annals of the New York Academy of Sciences

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Pathogen infections and dysregulated Toll-like receptor (TLR)-mediated innate immune responses are suspected to play key roles in autoimmunity. Among TLRs, TLR7 and TLR9 have been implicated in several autoimmune conditions, mainly because of their ability to promote abnormal B cell activation and survival. Recently, we provided evidence of Epstein-Barr virus (EBV) persistence and reactivation in the thymus of myasthenia gravis (MG) patients, suggesting an involvement of EBV in the intrathymic pathogenesis of the disease. Considerable data highlight the existence of pathogenic crosstalk among EBV, TLR7, and TLR9: EBV elicits TLR7/9 signaling, which in turn can enhance B cell dysfunction and autoimmunity. In this article, after a brief summary of data demonstrating TLR activation in MG thymus, we provide an overview on the contribution of TLR7 and TLR9 to autoimmune diseases and discuss our recent findings indicating a pivotal role for these two receptors, along with EBV, in driving, perpetuating, and/or amplifying intrathymic B cell dysregulation and autoimmune responses in MG. Development of therapeutic approaches targeting TLR7 and TLR9 signaling could be a novel strategy for treating the chronic inflammatory autoimmune process in myasthenia gravis.

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Section: Tlrs In Intrathymic Mg Pathogenesis: a Bridge Between Innatesupporting

confidence: 76%

Section: Tlrs In Intrathymic Mg Pathogenesis: a Bridge Between Innatementioning

confidence: 74%

Toll‐like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?

Cavalcante

Barzago

Baggi

et al. 2018

Annals of the New York Academy of Sciences

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“…In the case of LOMG, thymic abnormalities are rarely found [65], patients are predominantly male, antibodies against other proteins in the neuromuscular junction can also be found [63], and there is an increase of incidence in the last years of these patients [66]. These differences on clinical presentation are also in line with some findings that support differences in their underlying immune-mechanism [67], [68]. Despite the MG diversity, some authors suggest that MG is a single condition constituting a continuous clinical spectrum with overlapping features [65], [69].…”

Section: Discussionmentioning

confidence: 64%

Analysis of Serum miRNA Profiles of Myasthenia Gravis Patients

et al. 2014

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Myasthenia gravis (MG) is an autoimmune disease characterized by the presence of autoantibodies, mainly against the acetylcholine receptor (AChR). The mechanisms triggering and maintaining this chronic disease are unknown. MiRNAs are regulatory molecules that play a key role in the immune system and are altered in many autoimmune diseases. The aim of this study was to evaluate miRNA profiles in serum of 61 AChR MG patients. We studied serum from patients with early onset MG (n = 22), late onset MG (n = 27) and thymoma (n = 12), to identify alterations in the specific subgroups. In a discovery cohort, we analysed 381 miRNA arrays from 5 patients from each subgroup, and 5 healthy controls. The 15 patients had not received any treatment. We found 32 miRNAs in different levels in MG and analysed 8 of these in a validation cohort that included 46 of the MG patients. MiR15b, miR122, miR-140-3p, miR185, miR192, miR20b and miR-885-5p were in lower levels in MG patients than in controls. Our study suggests that different clinical phenotypes in MG share common altered mechanisms in circulating miRNAs, with no additional contribution of the thymoma. MG treatment intervention does not modify the profile of these miRNAs. Novel insights into the pathogenesis of MG can be reached by the analysis of circulating miRNAs since some of these miRNAs have also been found low in MG peripheral mononuclear cells, and have targets with important roles in B cell survival and antibody production.

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“…In the literature, MG is divided into EAMG and LOMG. However, there is no consensus on these definitions, with age thresholds of 40, 6,7 50 5,[8][9][10][11][12][13] or 60 years [14][15][16] in use, and various inclusion criteria for TAMG. We propose that TAMG should be separated, because this group is clinically distinct and has an aspect of paraneoplastic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Clinical features and treatment status of adult myasthenia gravis in Japan

Murai

Masuda

Utsugisawa

et al. 2014

Clinical & Exp Neuroim

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Objective Myasthenia gravis (MG) is classified as early-onset MG (EOMG; age at onset ≤49 years), late-onset MG (LOMG; age at onset ≥50 years) or thymoma-associated MG (TAMG) (E-L-T classification). To clarify the characteristics of each group in the E-L-T classification in Japan, we carried out multicenter analyses of MG. Methods A total of 640 adult patients from 11 MG centers participated in the study. Age at onset, sex, clinical symptoms, frequency of crisis, thymic pathology, positivity of autoantibodies against acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK), selected treatment, Cushingoid appearance and post-intervention status were evaluated in each group. Results EOMG, LOMG and TAMG accounted for 44%, 33%, and 23% of the patients, respectively. Females predominated in the EOMG group (77%), whereas there was no sex difference in the LOMG group. The frequency of ocular MG was the highest in the LOMG group (EOMG 15%, LOMG 38%, TAMG 12%). Bulbar symptoms and crisis were most frequent in the TAMG group. Anti-AChR antibody was always positive in patients with TAMG (EOMG 70%, LOMG 78%, TAMG 99%), whereas anti-MuSK antibody was never positive in TAMG patients, and more frequently detected in EOMG patients than in LOMG patients. Thymectomy was carried out in 51% of EOMG patients, 26% of LOMG patients and 97% of TAMG patients. Immunotherapy was carried out most aggressively in TAMG patients, and least aggressively in LOMG patients. Minimal manifestations or better with prednisolone ≤5 mg were achieved only in one-third of EOMG and TAMG patients. Conclusion Thymoma-associated MG required the most aggressive immunotherapy, followed by early-onset MG. (Clin. Exp. Neuroimmunol

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High anti‐EBNA‐1 IgG levels are associated with early‐onset myasthenia gravis

Abstract: In summary, our data suggest that high levels of EBNA-1 antibodies are more common in MG compared to healthy controls and are especially associated with EOMG.

Cited by 30 publications

References 18 publications

Toll‐like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?

Toll‐like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?

Analysis of Serum miRNA Profiles of Myasthenia Gravis Patients

Clinical features and treatment status of adult myasthenia gravis in Japan

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