Different molecular expression in thymoma with ocular or generalized myasthenia gravis

Zhang, Min; Li, Hongzeng; Guo, Jun; Zhou, Yunyun; Gong, Li; Wang, Xianni; Li, Zhuyi; Zhang, Wei

doi:10.1016/j.jns.2011.09.037

Cited by 8 publications

(2 citation statements)

References 26 publications

(30 reference statements)

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“…To analyze B cells and TECs as possible targets of EBV in thymoma, we firstly evaluated the degree of B cell infiltration in our thymoma samples, showing a higher number of B cells in MG versus non-MG thymomas, likely related to an increased expression of the B cell-attracting chemokine CXCL13 (Figure 3D ), in line with previous reports [ 47 – 49 ]. Here, we have frequently found co-localization of the latency EBV proteins LMP1 and LMP2A with the CD20-positive B cells in MG thymomas, but not in the non-MG tumor samples (Figure 4 ).…”

Section: Discussionsupporting

confidence: 68%

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

et al. 2017

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The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas. EBV DNA and EBV-encoded small nuclear RNA (EBER) 1 transcript were detected in 14/26 (53.8%) and 22/26 (84.6%) MG thymomas, and only in 3 of 14 (21.4%) non-MG thymomas. Latent EBNA2 and late gp350/220 lytic transcripts were undetectable in all, but one, thymomas, and early lytic BZLF1 transcript was absent in all samples, suggesting that early infection events and EBV reactivation were very rare in thymomas. EBER1 and 2-positive cells were detected in MG, but not in non-MG, thymomas, as well as cells expressing EBV latency proteins (EBNA1, LMP1, LMP2A), that were mainly of B cell phenotype, indicating EBV association with MG rather than with thymoma. Toll-like receptor (TLR) 3 transcriptional levels were higher in MG than non-MG thymomas and positively correlated with EBER1 levels, suggesting a role for EBERs in TLR3 activation. Our findings show that EBV is commonly present in thymoma-infiltrating B cells of myasthenic patients, indicating a contribution of EBV to B cell-mediated autoreactivity in MG associated with thymic tumor.

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Section: Discussionsupporting

confidence: 68%

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

et al. 2017

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“…In thymoma, lack of AIRE expression, absence of myoid cells, and failure to generate Tregs may all promote defective self-tolerance [67]. Recently, the expression of FoxP3 and the B-cell chemoattractant CXCL13 were found to vary with thymoma histology and myasthenia gravis subtype (generalized vs. ocular), prompting the proposal that different immunological processes underlie the two myasthenia gravis subtypes [68].…”

Section: Intrathymic Autoimmune Mechanismsmentioning

confidence: 99%

Autoimmune mechanisms in myasthenia gravis

Cavalcante

Bernasconi

Mantegazza

2012

Current Opinion in Neurology

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Expression of Immune Molecules CD25 and CXCL13 Correlated with Clinical Severity of Myasthenia Gravis

Zhang

Guo

et al. 2013

J Mol Neurosci

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Differential expressions of immune molecules have been shown in the thymi with pathological results, including myasthenia gravis (MG). CD25 is an activation marker expressed on T cells. CXCL13 mediates the homing and motility of B cells in secondary lymphoid tissues. Herein, we investigated the expressions of CD25 and CXCL13 in the thymi of thymic hyperplasia patients with MG or with non-MG. A total of 34 thymic hyperplasia patients with MG (20 generalized MG (GMG) and 14 ocular MG (OMG) and six thymic hyperplasia patients without MG were enrolled and analyzed using immunohistochemical staining and real-time polymerase chain reaction for CD25 and CXCL13. Our study demonstrated a higher expression of both CD25 and CXCL13 in hyperplastic thymi with OMG or GMG compared to those with non-MG. According to the immunohistochemical results, we observed that CD25 expression was significantly lower in atrophic thymi and non-MG hyperplastic thymi, compared with that in infant thymi (P = 0.002 and 0.005, respectively). In contrast to CD25 expression, we did not observe differential expression of CXCL13 among three control groups. And a similar CD25 mRNA expression was found in real-time polymerase chain reaction (PCR) results. We observed that both hyperplastic thymi with OMG or GMG expressed significantly higher levels of CD25 than those with non-MG (P = 0.007 and 0.001, respectively). And an increase of CD25 expression was observed in hyperplastic thymi with GMG compared to those with OMG (P = 0.030). Similarly, CXCL13 expression was significantly higher in hyperplastic thymi with GMG or with OMG than those with non-MG (P = 0.001 and 0.050, respectively). No significant CXCL13 expression difference was found between hyperplastic thymi with GMG and those with OMG (P > 0.05). The real-time PCR results showed a similar tendency of CD25 mRNA expression among the thymi of non-MG, OMG, and GMG patients, but the difference did not reach significance (P > 0.05). An obvious increased expression of CXCL13 was found in hyperplastic thymi with GMG patients, compared to those with non-MG and OMG patients (P = 0.003 and 0.071, respectively). There was no difference found between hyperplastic thymi with non-MG and with OMG. Regression analysis showed a positive correlation between thymic CD25 level and MG symptom severity (F = 28.240; P = 0.000, r = 0.523). Similarly, a positive correlation was found between thymic CXCL13 expression and MG disease severity (F = 36.093; P = 0.000, r = 0.671). Taken together, our findings suggest CD25 and CXCL13 participate in the pathogenesis of MG and may influence the clinical symptoms of MG.

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Different molecular expression in thymoma with ocular or generalized myasthenia gravis

Cited by 8 publications

References 26 publications

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

Autoimmune mechanisms in myasthenia gravis

Expression of Immune Molecules CD25 and CXCL13 Correlated with Clinical Severity of Myasthenia Gravis

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