Thymus involvement in early‐onset myasthenia gravis

Cron, Mélanie A.; Maillard, Solène; Villegas, José Adolfo; Truffault, Frédérique; Sudres, Muriel; Dragin, Nadine; Berrih‐Aknin, Sonia; Panse, Rozen Le

doi:10.1111/nyas.13519

Cited by 81 publications

(62 citation statements)

References 72 publications

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“…Both miR-150-5p and miR-21-5p are so-called immuno-miRs and considered important T cell regulators (71). In AChR+ EOMG, the effector organ is the thymus, which is often characterized by hyperplasia as well as ectopic germinal centers consisting of infiltrating B cells (9,72). miR-150 regulates proliferation, apoptosis, and differentiation of natural killer (NK), T, and B cells (71,73,74) and is a marker of lymphocyte activation (75).…”

Section: Link Between Elevated Circulating Mirnas In Mg and Disease Pmentioning

confidence: 99%

“…MG patients suffer from fluctuating skeletal muscle fatigue and weakness. The etiology of the disease is unknown, although the thymus is considered to play a central role in the disease process as it is essential for T cell differentiation and the establishment of central tolerance (8,9). Valid diagnostic measures for MG include antibody analysis, electrophysiological measures of impaired neuromuscular transmission, and objective clinical evaluation of skeletal muscle fatigue, such as the quantitative MG (QMG) score or MG composite (MGC) score.…”

Section: Introductionmentioning

confidence: 99%

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Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine

Sabre

Punga

2020

Front. Immunol.

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Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack receptors at the neuromuscular junction. One of the main difficulties in predicting the clinical course of MG is the heterogeneity of the disease, where disease progression differs greatly depending on the subgroup that the patient is classified into. MG subgroups are classified according to: age of onset [early-onset MG (EOMG; onset ≤ 50 years) versus late-onset MG (LOMG; onset > 50 years]; the presence of a thymoma (thymoma-associated MG); antibody subtype [acetylcholine receptor antibody seropositive (AChR+) and muscle-specific tyrosine kinase antibody seropositive (MuSK+)]; as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue score, do not necessarily reflect disease progression. Hence, there is a great need for reliable objective biomarkers in MG to follow the disease course as well as the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patients' sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, the miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decrease in accordance with the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody-seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.

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Section: Link Between Elevated Circulating Mirnas In Mg and Disease Pmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine

Sabre

Punga

2020

Front. Immunol.

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“…Thymus is a well‐known organ critical for the induction of central immune tolerance 4,15 . Thymic dysfunction could lead to MG, a T cell‐mediated autoimmune disorder affecting neuromuscular junction 2,16 . Advances have been made in the understanding of the involvement of lncRNAs in the pathogenesis of MG 17,18 .…”

Section: Discussionmentioning

confidence: 99%

“…Myasthenia gravis (MG) is an autoimmune disease caused by neuromuscular transmission disorder mediated by acetylcholine receptor (AChR)‐specific T lymphocytes 1 . There is emerging evidence that the pathogenesis of MG involves the functional status of the thymus gland 2 . More importantly, MG patients have a high risk of developing thymic lesions, including thymoma, thymic hyperplasia and thymic atrophy 3 .…”

Section: Introductionmentioning

confidence: 99%

LncRNA XLOC_003810 promotes T cell activation and inhibits PD‐1/PD‐L1 expression in patients with myasthenia gravis‐related thymoma

Niu

Jiang

et al. 2020

Scand J Immunol

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This study aimed to investigate the effect of long non‐coding RNA XLOC_003810 on the activation of CD4+ T cells and expression of PD‐1/PD‐L1 in patients with myasthenia gravis‐related thymoma (MG‐T). Thymus specimens and thymic mononuclear cells were obtained from MG and MG‐T patients or cardiac surgery patients undergoing thoracotomy who were selected as negative controls (NC). XLOC_003810 expression was examined using quantitative real‐time PCR (qRT‐PCR). Frequency of CD4+ T cells and proportion of CD4+PD‐1+ T cells and CD14+PD‐L1+ monocytes were quantified by flow cytometry. The release of inflammatory cytokines was measured by qRT‐PCR and enzyme‐linked immunosorbent assay. Compared with the NC group, expression of XLOC_003810, frequency of CD4+ T cells and the production of inflammatory cytokines were increased in patients with MG and MG‐T. XLOC_003810 overexpression significantly increased the frequency of CD4+ T cells, facilitated the production of inflammatory cytokines and decreased the proportion of CD4+PD‐1+ T cells and CD14+PD‐L1+ monocytes in the thymic mononuclear cells. In contrast, XLOC_003810 knockdown exerted the opposite effect. Together, XLOC_003810 promotes T cell activation and inhibits PD‐1/PD‐L1 pathway in patients with MG‐T.

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“…It is well-known that genetic predispositions exist in MG patients ( 9 ), however, additional epigenetic changes occur. The expression of small non-coding RNA, microRNA (miRNA), is dysregulated in the thymus of AChR + MG patients ( 10 , 11 ) and could be involved in thymic changes associated with MG, linked to thymic inflammation and ectopic germinal center development ( Bortone et al; Cron et al ). Circulating miRNAs are also potential biomarkers since they are differentially expressed in the serum of MG patients ( Sabre et al ).…”

mentioning

confidence: 99%