Viral infection in thymoma and thymic tumors with autoimmune diseases

Chang, R. P. H.; Duan, Shuning; Li, Shicong; Zhang, Peng

doi:10.1111/1759-7714.14157

Cited by 6 publications

(10 citation statements)

References 72 publications

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“…The other function of HVEM is that it mediates the entry of herpes simplex virus type 1 (HSV-1) and HSV-2 into cells, which do not include other subtypes such as Epstein–Barr (EB) virus and varicella zoster virus (VZV) ( 38 ). We think that this might explain why fewer HSV-infected MG patient cases were reported than those EB and VZV cases in clinical settings ( 39 , 40 ). However, studies with larger sample size and stringent design are needed to validate this in future.…”

Section: Discussionmentioning

confidence: 99%

Herpesvirus entry mediator on T cells as a protective factor for myasthenia gravis: A Mendelian randomization study

et al. 2022

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Background and objectivesMyasthenia gravis (MG) is a T cell-driven, autoantibody-mediated disorder affecting transmission in neuromuscular junctions. The associations between the peripheral T cells and MG have been extensively studied. However, they are mainly of observational nature, thus limiting our understanding of the effect of inflammatory biomarkers on MG risk. With large data sets now available, we used Mendelian randomization (MR) analysis to investigate whether the biomarkers on T cells are causally associated with MG and further validate the relationships.MethodsWe performed a two-sample MR analysis using genetic data from one genome-wide association study (GWAS) for 210 extensive T-cell traits in 3,757 general population individuals and the largest GWAS for MG currently available (1,873 patients versus 36,370 age/gender-matched controls) from US and Italy. Then the biomarkers of interest were validated separately in two GWASs for MG in FIN biobank (232 patients versus 217,056 controls) and UK biobank (152 patients versus 386,631 controls).ResultsIn the first analysis, three T-cell traits were identified to be causally protective for MG risk: 1) CD8 on terminally differentiated CD8+ T cells (OR [95% CI] = 0.71 [0.59, 0.86], P = 5.62e-04, adjusted P =2.81e-02); 2) CD4+ regulatory T proportion in T cells (OR [95% CI] = 0.44 [0.26, 0.72], P = 1.30e-03, adjusted P =2.81e-02); 3) HVEM expression on total T cells (OR [95% CI] = 0.67 [0.52, 0.86], P = 1.61e-03, adjusted P =2.81e-02) and other eight T-cell subtypes (e.g., naïve CD4+ T cells). In particular, HVEM is a novel immune checkpoint on T cells that has never been linked to MG before. The SNPs on the TNFRSF14 per se further support a more direct link between the HVEM and MG. The validation analysis replicated these results in both FIN and UK biobanks. Both datasets showed a concordant protective trend supporting the findings, albeit not significant.ConclusionThis study highlighted the role of HVEM on T cells as a novel molecular-modified factor for MG risk and validated the causality between T cells and MG. These findings may advance our understanding of MG’s immunopathology and facilitate the future development of predictive disease-relevant biomarkers.

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Section: Discussionmentioning

confidence: 99%

Herpesvirus entry mediator on T cells as a protective factor for myasthenia gravis: A Mendelian randomization study

et al. 2022

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“…The relationships between viral infections, thymoma, and autoimmune disorders such as autoimmune encephalitis are becoming increasingly well‐recognized. Prior studies have implicated varicella‐zoster virus, herpes simplex virus, and Epstein–Barr virus as contributing pathogens to triggering thymoma‐associated autoimmune disorders, 4 but we would like to highlight the first case of AMPA‐R and CRMP‐5 encephalitis associated with concurrent SARS‐CoV‐2 infection. COVID‐19 has commonly been associated with encephalopathy, but rarely seronegative autoimmune encephalitis has also been described 8,9 .…”

Section: Discussionmentioning

confidence: 99%

“…The association between thymomas and autoimmune encephalitis is less well‐known, although prior literature suggests a poorer prognosis 3 . More recently, the possibility that viral infections may contribute to the pathogenesis of autoimmune/paraneoplastic disorders in patients with coexisting thymomas has been raised, although the exact mechanism is still unclear 4 …”

Section: Introductionmentioning

confidence: 99%

“…3 More recently, the possibility that viral infections may contribute to the pathogenesis of autoimmune/ paraneoplastic disorders in patients with coexisting thymomas has been raised, although the exact mechanism is still unclear. 4 Here, we describe a case of αamino-3-hydroxy-5methyl-4-isoxazolepropionic acid receptor (AMPA-R) and collapsin response mediator protein 5 (CRMP-5) antibodypositive autoimmune encephalitis that developed in a patient with acetylcholine receptor (AChR)-positive MG with a known thymoma in the setting of COVID-19. While the presence of a thymoma is known to be associated with the development of autoimmune encephalitis, the temporal association with SARS-CoV-2 infection suggested that this may have triggered additional autoantibody production in our patient.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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