Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis

Zekeridou A, McKeon A, Lennon VA. Frequency of synaptic autoantibody accompaniments and neurological manifestations of Thymoma. JAMA Neurol. 2016;73:853–9.

Article  PubMed  Google Scholar 

Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to the 2015 World Health Organization Classification of Tumors of the lung, Pleura, Thymus, and heart. J Thorac Oncol. 2015;10:1240–2.

Article  PubMed  Google Scholar 

Cufi P, Dragin N, Ruhlmann N, Weiss JM, Fadel E, Serraf A, Berrih-Aknin S, Le Panse R. Central role of interferon-beta in thymic events leading to myasthenia gravis. J Autoimmun. 2014;52:44–52.

Article  CAS  PubMed  Google Scholar 

Cufi P, Soussan P, Truffault F, Fetouchi R, Robinet M, Fadel E, Berrih-Aknin S, Le Panse R. Thymoma-associated myasthenia gravis: on the search for a pathogen signature. J Autoimmun. 2014;52:29–35.

Article  CAS  PubMed  Google Scholar 

Strobel P, Murumagi A, Klein R, Luster M, Lahti M, Krohn K, Schalke B, Nix W, Gold R, Rieckmann P, et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J Pathol. 2007;211:563–71.

Article  CAS  PubMed  Google Scholar 

Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Strobel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12:875–84.

Article  CAS  PubMed  Google Scholar 

Marx A, Porubsky S, Belharazem D, Saruhan-Direskeneli G, Schalke B, Strobel P, Weis CA. Thymoma related myasthenia gravis in humans and potential animal models. Exp Neurol. 2015;270:55–65.

Article  PubMed  Google Scholar 

Scarpino S, Di Napoli A, Stoppacciaro A, Antonelli M, Pilozzi E, Chiarle R, Palestro G, Marino M, Facciolo F, Rendina EA, et al. Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas. Clin Exp Immunol. 2007;149:504–12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suzuki E, Kobayashi Y, Yano M, Fujii Y. Infrequent and low AIRE expression in thymoma: difference in AIRE expression among WHO subtypes does not correlate with association of MG. Autoimmunity. 2008;41:377–82.

Article  CAS  PubMed  Google Scholar 

Iacomino N, Scandiffio L, Conforti F, Salvi E, Tarasco MC, Bortone F, Marcuzzo S, Simoncini O, Andreetta F, Pistillo D, et al. Muscle and muscle-like Autoantigen expression in Myasthenia gravis Thymus: possible molecular hint for autosensitization. Biomedicines. 2023;11:732.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luther C, Adamopoulou E, Stoeckle C, Brucklacher-Waldert V, Rosenkranz D, Stoltze L, Lauer S, Poeschel S, Melms A, Tolosa E. Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients. J Immunol. 2009;183:841–8.

Article  CAS  PubMed  Google Scholar 

Strobel P, Rosenwald A, Beyersdorf N, Kerkau T, Elert O, Murumagi A, Sillanpaa N, Peterson P, Hummel V, Rieckmann P, et al. Selective loss of regulatory T cells in thymomas. Ann Neurol. 2004;56:901–4.

Article  PubMed  Google Scholar 

Hoffacker V, Schultz A, Tiesinga JJ, Gold R, Schalke B, Nix W, Kiefer R, Muller-Hermelink HK, Marx A. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood. 2000;96:3872–9.

Article  CAS  PubMed  Google Scholar 

Buckley C, Douek D, Newsom-Davis J, Vincent A, Willcox N. Mature, long-lived CD4 + and CD8 + T cells are generated by the thymoma in myasthenia gravis. Ann Neurol. 2001;50:64–72.

Article  CAS  PubMed  Google Scholar 

Strobel P, Helmreich M, Menioudakis G, Lewin SR, Rudiger T, Bauer A, Hoffacker V, Gold R, Nix W, Schalke B, et al. Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood. 2002;100:159–66.

Article  CAS  PubMed  Google Scholar 

Balandina A, Saoudi A, Dartevelle P, Berrih-Aknin S. Analysis of CD4 + CD25 + cell population in the thymus from myasthenia gravis patients. Ann N Y Acad Sci. 2003;998:275–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luther C, Poeschel S, Varga M, Melms A, Tolosa E. Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma. J Neuroimmunol. 2005;164:124–8.

Article  CAS  PubMed  Google Scholar 

Kohler S, Keil TOP, Hoffmann S, Swierzy M, Ismail M, Ruckert JC, Alexander T, Meisel A. CD4(+) FoxP3(+) T regulatory cell subsets in myasthenia gravis patients. Clin Immunol. 2017;179:40–6.

Article  CAS  PubMed  Google Scholar 

Chen Y, Zhang XS, Wang YG, Lu C, Li J, Zhang P. Imbalance of Th17 and Tregs in Thymoma may be a pathological mechanism of myasthenia gravis. Mol Immunol. 2021;133:67–76.

Article  CAS  PubMed  Google Scholar 

Cebi M, Cakar A, Erdogdu E, Durmus-Tekce H, Yegen G, Ozkan B, Parman Y, Saruhan-Direskeneli G. Thymoma patients with or without myasthenia gravis have increased Th17 cells, IL-17 production and ICOS expression. J Neuroimmunol. 2023;381:578129.

Article  CAS  PubMed  Google Scholar 

Gradolatto A, Nazzal D, Truffault F, Bismuth J, Fadel E, Foti M, Berrih-Aknin S. Both Treg cells and tconv cells are defective in the Myasthenia gravis thymus: roles of IL-17 and TNF-alpha. J Autoimmun. 2014;52:53–63.

Article  CAS  PubMed  Google Scholar 

Villegas JA, Bayer AC, Ider K, Bismuth J, Truffault F, Roussin R, Santelmo N, Le Panse R, Berrih-Aknin S, Dragin N. Il-23/Th17 cell pathway: a promising target to alleviate thymic inflammation maintenance in myasthenia gravis. J Autoimmun. 2019;98:59–73.

Article  CAS  PubMed  Google Scholar 

Masoud GN, Li W. HIF-1alpha pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B. 2015;5:378–89.

Article  PubMed  PubMed Central  Google Scholar 

Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146:772–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marx A, Chan JKC, Chalabreysse L, Dacic S, Detterbeck F, French CA, Hornick JL, Inagaki H, Jain D, Lazar AJ, et al. The 2021 WHO classification of tumors of the Thymus and Mediastinum: what is New in Thymic Epithelial, Germ Cell, and mesenchymal tumors? J Thorac Oncol. 2022;17:200–13.

Article  PubMed  Google Scholar 

Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, Moorman AF. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009;37:e45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo F, Wang CY, Wang S, Zhang J, Yan YJ, Guan ZY, Meng FJ. Alteration in gene expression profile of thymomas with or without myasthenia gravis linked with the nuclear factor-kappaB/autoimmune regulator pathway to myasthenia gravis pathogenesis. Thorac Cancer. 2019;10:564–70.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010;40:294–309.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Appelhoff RJ, Tian YM, Raval RR, Turley H, Harris AL, Pugh CW, Ratcliffe PJ, Gleadle JM. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Biol Chem. 2004;279:38458–65.

Article  CAS  PubMed  Google Scholar 

Lee JW, Bae SH, Jeong JW, Kim SH, Kim KW. Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp Mol Med. 2004;36:1–12.

Article  PubMed  Google Scholar 

Capone A, Volpe E. Transcriptional regulators of T Helper 17 cell differentiation in Health and Autoimmune diseases. Front Immunol. 2020;11:348.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Filì L, Ferri S, Frosali F, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chinen T, Kannan AK, Levine AG, Fan X, Klein U, Zheng Y, Gasteiger G, Feng Y, Fontenot JD, Rudensky AY. An essential role for the IL-2 receptor in T(reg) cell function. Nat Immunol. 2016;17:1322–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016;375:2570–81.

Article  CAS 

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