Lack of Epstein-Barr virus infection in Chinese myasthenia gravis patients

Jin, Feng; Ding, Wei; Wang, D.; Li, N.; Cui, Fang; Yun, Fan; Chen, Z.; Huang, Xusheng

doi:10.1111/ane.12124

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…EBV is one of the most concerning viruses in the literature regarding the correlation between viruses and MG with thymus abnormalities, but the role of EBV in the pathogenesis of MG remains controversial. 6 - 10 Thus, in this study, we mainly explored the role of B19V, a virus playing a similar role to EBV in autoimmune diseases, in thymoma, and further investigated EBV status. B19V was first discovered by Cossart et al in 1975.…”

Section: Discussionmentioning

confidence: 99%

“…In general, chronic inflammation of the thymus caused by a viral or bacterial infection may trigger the development of autoimmunity, generally by activating the host immune system and molecular mimicry, thereby contributing to the pathogenesis of MG. Some studies have demonstrated that intrathymus Epstein–Barr virus (EBV) infection is an environmental risk factor for MG. 6 , 7 However, an increasing number of studies have reported a lack of evidence for EBV infection in the thymus of patients with MG. 8 - 10 Hence, the role of EBV in the pathogenesis of MG remains controversial.…”

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confidence: 99%

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Human Parvovirus B19 May Be a Risk Factor in Myasthenia Gravis with Thymoma

et al. 2022

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Purpose Our previous studies have demonstrated that human parvovirus B19 (B19V) is involved in the pathogenesis of thymic hyperplasia-associated myasthenia gravis (MG). However, more cases need to be assessed to further elucidate the relationship between this virus and thymoma-associated MG. Materials and Methods The clinicopathological characteristics, presence of B19V DNA, and B19V VP2 capsid protein expression of 708 cases of thymomas were investigated using nested polymerase chain reaction (PCR), TaqMan quantitative (q) PCR, immunohistochemistry, fluorescent multiplex immunohistochemistry, and electron microscopy. Results Patients with MG or ectopic germinal centers (GCs) were significantly younger than those without MG ( P < 0.0001) or GCs ( P = 0.0001). Moreover, significantly more GCs were detected in thymomas associated with MG than in those without MG ( P < 0.0001). The results of nested PCR and TaqMan qPCR were consistent, and B19V DNA positivity was only associated with presence of GCs ( P = 0.011). Immunohistochemically, positive staining was primarily detected in neoplastic thymic epithelial cells (TECs) and ectopic GCs. The positive rate of B19V VP2 was significantly higher in thymoma with MG or GCs than in thymoma without MG ( P = 0.004) or GCs ( P = 0.006). Electron microscopy showed B19V particles in the nuclei of neoplastic TECs and B cells from GCs. Conclusions We conclude that the pathogenesis of MG is closely associated with the presence of GCs, and B19V infection is plausibly an essential contributor to formation of ectopic GCs in thymoma. To the best of the authors’ knowledge, this is the first study to elucidate the role of B19V in thymoma-associated MG and provide new ideas for exploring the etiopathogenic mechanism of MG. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-022-12936-9.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Human Parvovirus B19 May Be a Risk Factor in Myasthenia Gravis with Thymoma

et al. 2022

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“…assessedNo. positive1988McGuire et al [13]ChinaSBHT, LT, TIMG1161990Inghirami et al [14]USA, ItalySBH, PCRTMG1601990Borisch et al [15]GermanyISH, SBHNT, THMG5101992Mann et al [16]USAISHLT, T/TC–40/70/11993Wu et al [17]ChinaISHT/TC–21/200/11993Fujii et al [18]JapanISHT/TC–7/80/12000Hishima et al [19]JapanISHT/TC–18/902000Engel et al [20]DenmarkISHT/TC–105/5202001Tateyama et al [21]JapanISHT/TC–9/24/12002Chen et al [22]ChinaISH, PCRT/TC–78/210/62010Cavalcante et al [6]ItalyISH, IH, PCRTH, LT, TIMG17172011Meyer et al [8]GermanyISH, IHLTMG4402011Cavalcante et al [7]ItalyPCRTH, LT, TIMG19122011Kakalacheva et al [9]EuropeISH, IH, PCRLTMG1612013Jing et al [23]ChinaISH,...…”

Section: Resultsmentioning

confidence: 99%

Association between Epstein-Barr virus and Thymic epithelial tumors: a systematic review

Zhang

Shen

et al. 2019

Infect Agents Cancer

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The possible role of Epstein-Barr virus (EBV) in the pathogenesis of thymic epithelial tumors (TET) remains controversial. This study aimed to determine the prevalence of EBV in TET. We conducted a systematic review of relevant English-language studies published between January 1980 and December 2013. Effect size was calculated as event rates (95% confidence interval [CI]) by homogeneity testing using Cochran’s Q and I2 statistics for benign TET, benign TET with myasthenia gravis (MG), and thymic carcinoma (TC). Among 136 potentially relevant studies, 22 met the inclusion criteria. Despite a considerable degree of heterogeneity, the pooled estimated incidences were 9% (95% CI, 1–23%), 20% (95% CI, 0–54%), and 6% (95% CI, 0–21%) for benign TET, benign TET with MG, and TC, respectively. There was significant heterogeneity among studies that used in situ hybridization (ISH) for both benign TET and benign TET with MG. According to the random-effects model, studies employing ISH yielded lower point estimates of EBV prevalence (5%) than those employing other methods (33%). Using the random-effects model, we found a lack of significant heterogeneity among studies from different geographic regions (p = 0.0848). Further, 12 of 23 lymphoepithelioma-like carcinoma (LELC) cases tested EBV-positive. The prevalence of EBV in benign TET with or without MG was lower than in nasopharyngeal carcinoma, suggesting that EBV plays a minor role in TET pathogenesis. Although the prevalence of EBV in TC was also low, EBV may play an important causal role in LELC. Further research is needed to clarify these associations.

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“…The EBVinduced TLR7/9 signaling pathway-mediated immune response might play a role in the progression of MG [54]. However, Meyer et al and Jing et al reported no evidence of EBV association with MG thymus contradicting the previous studies [55,56]. Other studies also indicate the role of cytomegalovirus, human foamy virus (HFV), and Nile virus in the progression of MG [33,57].…”

Section: Etiological Factors and Pathophysiologymentioning

confidence: 95%

Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions

Huang¹,

Wu²,

Wang³

et al. 2022

Aging and disease

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The prevalence of myasthenia gravis (MG), an autoimmune disorder, is increasing among all subsets of the population leading to an elevated economic and social burden. The pathogenesis of MG is characterized by the synthesis of autoantibodies against the acetylcholine receptor (AChR), low-density lipoprotein receptor-related protein 4 (LRP4), or muscle-specific kinase at the neuromuscular junction, thereby leading to muscular weakness and fatigue. Based on clinical and laboratory examinations, the research is focused on distinguishing MG from other autoimmune, genetic diseases of neuromuscular transmission. Technological advancements in machine learning, a subset of artificial intelligence (AI) have been assistive in accurate diagnosis and management. Besides, addressing the clinical needs of MG patients is critical to improving quality of life (QoL) and satisfaction. Lifestyle changes including physical exercise and traditional Chinese medicine/herbs have also been shown to exert an ameliorative impact on MG progression. To achieve enhanced therapeutic efficacy, cholinesterase inhibitors, immunosuppressive drugs, and steroids in addition to plasma exchange therapy are widely recommended. Under surgical intervention, thymectomy is the only feasible alternative to removing thymoma to overcome thymoma-associated MG. Although these conventional and current therapeutic approaches are effective, the associated adverse events and surgical complexity limit their wide application. Moreover, Restivo et al. also, to increase survival and QoL, further recent developments revealed that antibody, gene, and regenerative therapies (such as stem cells and exosomes) are currently being investigated as a safer and more efficacious alternative. Considering these above-mentioned points, we have comprehensively reviewed the recent advances in pathological etiologies of MG including COVID-19, and its therapeutic management.

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Lack of Epstein-Barr virus infection in Chinese myasthenia gravis patients

Abstract: Our results therefore do not support a role of thymic Epstein-Barr virus infection in myasthenia gravis pathogenesis and calls for an integration of methodological and interpretation issues in detecting Epstein-Barr virus incidence in myasthenia gravis patients.

Cited by 5 publications

References 26 publications

Human Parvovirus B19 May Be a Risk Factor in Myasthenia Gravis with Thymoma

Human Parvovirus B19 May Be a Risk Factor in Myasthenia Gravis with Thymoma

Association between Epstein-Barr virus and Thymic epithelial tumors: a systematic review

Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions

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