A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients

Barzago, Claudia; Lum, Josephine; Cavalcante, Paola; Srinivasan, Kandhadayar G.; Faggiani, Elisa; Camera, Giorgia; Bonanno, Silvia; Andreetta, Francesca; Antozzi, Carlo; Baggi, Fulvio; Calogero, Raffaele; Bernasconi, Pia; Mantegazza, Renato; Mori, Lucia; Zolezzi, Francesca

doi:10.1016/j.imbio.2016.06.012

Cited by 34 publications

(25 citation statements)

References 54 publications

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“…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 . These results, along with literature data showing overexpression of some TLRs, including TLR3, TLR4, TLR8, and TLR9, in PBMCs of MG patients, 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 Innatesupporting

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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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: 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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“…However, no further detailed investigations were reported for the two gastrointestinal cancers, and this is the first time, to our knowledge, that we present its role as a biomarker for HCC. Additionally, in myasthenia gravis, the miR-3651's putative target-CRISP3 (cysteine-rich secretory protein 3), plays an important role in innate immune response, which indicate it may be a vital regulatory factor in immunological process (Barzago et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Zhu

Huang

et al. 2018

Tohoku J. Exp. Med.

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Hepatocellular carcinoma (HCC) remains a major health problem for delayed diagnosis, inefficient surveillance and poor prognosis. Recent studies have indicated that non-coding RNAs contribute to the development of new strategies for diagnosis and treatment of HCC. In the present study, we employed 18 pairs of HCC and matched non-tumor tissues for the identification of differentially expressed microRNAs (miRNAs) in HCC, among which 7 paired specimens were selected randomly for microarray detection. Totally, twenty-three miRNAs were screened out to have statistically significant differences with the threshold of P < 0.01 and fold-change ≥ 2.0 or ≤ 0.5 using miRNA microarray. In the validation stage, two miRNAs exhibited higher expression levels in the HCC tissues compared with those in the matched non-tumor tissues, whereas the expression levels of ten miRNAs were lower in the HCC tissues than those in the matched non-tumor tissues. In further analysis, eight miRNAs, including miR-4270, miR-125b-5p, miR-199a-3p, miR-10a-5p, miR-424-5p, miR-195-5p, miR-106b-5p and miR-3651, were retained, when another constraint about the signal intensity of microarray probes was established. Among these miRNAs, our study was the first to show the higher expression level of miR-3651 and the lower expression level of miR-4270 in HCC. The areas under the receiver-operating-characteristic curve values of miR-3651 and miR-4270 were 0.730 and 0.967, respectively, indicating their potential diagnostic values. Our results may help provide the context for expanded interpretations of miRNA studies involved in the progression of liver disease, potentially serving as a diagnostic tool of HCC.

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“…In myasthenic patients, the existence of a chronic inflammatory state in the thymus could alter innate immune responses leading to self-tolerance failure (36–39). The inflammatory state could be due to persistent viral replications, in fact, Epstein Barr virus (EBV), cytomegalovirus, human foamy virus, and Nile virus were found to be associated to MG (40, 41). Pathogen infections could play a role in AIDs through dysregulation of toll-like receptor-mediated innate immune responses, which can result in altered innate immune responses and long-term inflammation, rendering the thymus vulnerable to auto-sensitization (40, 41).…”

Section: Etiologymentioning

confidence: 99%

“…The inflammatory state could be due to persistent viral replications, in fact, Epstein Barr virus (EBV), cytomegalovirus, human foamy virus, and Nile virus were found to be associated to MG (40, 41). Pathogen infections could play a role in AIDs through dysregulation of toll-like receptor-mediated innate immune responses, which can result in altered innate immune responses and long-term inflammation, rendering the thymus vulnerable to auto-sensitization (40, 41). EBV is one of the main candidates suspected to play a role in MG initiation, since it is able to promote B-cell abnormal activation and survival, and to disrupt critical B-cell tolerance checkpoints (40, 42–44).…”

Section: Etiologymentioning

confidence: 99%

Autoimmune Thyroiditis and Myasthenia Gravis

Lopomo

Berrih‐Aknin

2017

Front. Endocrinol.

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Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed.

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A novel infection- and inflammation-associated molecular signature in peripheral blood of myasthenia gravis patients

Cited by 34 publications

References 54 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?

Microarray Expression Profiling of microRNAs Reveals Potential Biomarkers for Hepatocellular Carcinoma

Autoimmune Thyroiditis and Myasthenia Gravis

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