Thymectomy lowers the myasthenia gravis biomarker miR-150-5p

被引:32
作者
Molin, Carl Johan [1 ]
Sabre, Liis [1 ]
Weis, Cleo-Aron [2 ]
Punga, Tanel [3 ]
Punga, Anna Rostedt [1 ]
机构
[1] Uppsala Univ, Dept Neurosci, Clin Neurophysiol, Uppsala, Sweden
[2] Heidelberg Univ, Med Fac Mannheim, Univ Med Ctr Mannheim, Inst Pathol, Heidelberg, Germany
[3] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden
基金
瑞典研究理事会;
关键词
T-CELL DEVELOPMENT; CIRCULATING MICRORNAS; THYMUS; SIGNATURE; TRIAL;
D O I
10.1212/NXI.0000000000000450
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective The aim of the study was to analyze the effect of thymectomy on the proposed disease-specific microRNA (miRNA) biomarkers miR-150-5p and miR-21-5p in patients from the prospective randomized trial of thymectomy in myasthenia gravis (MGTX trial) and to evaluate the longitudinal changes in clinical patterns compared with these miRNA levels. Methods Serum samples were obtained from 80 patients with MG who were included in the MGTX trial. Thirty-eight patients were randomized to thymectomy plus prednisone treatment, and 42 patients were randomized to prednisone treatment. Serum samples were analyzed for the expression of miR-150-5p and miR-21-5p, with quantitative reverse transcriptase PCR at baseline and at 12, 24, and 36 months after randomization. The inclusion criteria for participation in the MGTX trial were age 18-65 years, generalized myasthenia gravis (Myasthenia Gravis Foundation of America Class II-IV), disease duration of less than 5 years, and seropositivity for acetylcholine receptor antibodies (AChR+). Results Patients treated with thymectomy had lower levels of miR-150-5p at 24 months, both compared with baseline values (p = 0.0011) and the prednisone group (p = 0.04). No change in miRNA levels was found in the prednisone group. Levels of miR-21-5p displayed a negative correlation with the prednisone dose within the prednisone-only group (p <= 0.001). Conclusions Thymectomy lowers the levels of the proposed biomarker miR-150-5p, which strengthens its position as a potential disease-specific biomarker for AChR+ MG.
引用
收藏
页数:8
相关论文
共 26 条
[1]   Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis [J].
Balandina, A ;
Lécart, S ;
Dartevelle, P ;
Saoudi, A ;
Berrih-Aknin, S .
BLOOD, 2005, 105 (02) :735-741
[2]   Recommendations for myasthenia gravis clinical trials [J].
Benatar, Michael ;
Sanders, Donald B. ;
Burns, Ted M. ;
Cutter, Gary R. ;
Guptill, Jeffrey T. ;
Baggi, Fulvio ;
Kaminski, Henry J. ;
Mantegazza, Renato ;
Meriggioli, Matthew N. ;
Quan, Joanne ;
Wolfe, Gil I. .
MUSCLE & NERVE, 2012, 45 (06) :909-917
[3]   Diagnostic and clinical classification of autoimmune myasthenia gravis [J].
Berrih-Aknin, Sonia ;
Frenkian-Cuvelier, Melinee ;
Eymard, Bruno .
JOURNAL OF AUTOIMMUNITY, 2014, 48-49 :143-148
[4]   Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis [J].
Evoli, A ;
Tonali, PA ;
Padua, L ;
Lo Monaco, M ;
Scuderi, F ;
Batocchi, AP ;
Marino, M ;
Bartoccioni, E .
BRAIN, 2003, 126 :2304-2311
[5]   Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150 [J].
Ghisi, Margherita ;
Corradin, Alberto ;
Basso, Katia ;
Frasson, Chiara ;
Serafin, Valentina ;
Mukherjee, Subhamoy ;
Mussolin, Lara ;
Ruggero, Katia ;
Bonanno, Laura ;
Guffanti, Alessandro ;
De Bellis, Gianluca ;
Gerosa, Gino ;
Stellin, Giovanni ;
D'Agostino, Donna M. ;
Basso, Giuseppe ;
Bronte, Vincenzo ;
Indraccolo, Stefano ;
Amadori, Alberto ;
Zanovello, Paola .
BLOOD, 2011, 117 (26) :7053-7062
[6]   Myasthenia Gravis [J].
Gilhus, Nils E. .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (26) :2570-2581
[7]   Regulation of microRNA biogenesis [J].
Ha, Minju ;
Kim, V. Narry .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (08) :509-524
[8]   Can circulating miRNAs live up to the promise of being minimal invasive biomarkers in clinical settings? [J].
Keller, Andreas ;
Meese, Eckart .
WILEY INTERDISCIPLINARY REVIEWS-RNA, 2016, 7 (02) :148-156
[9]   Immuno-miRs: critical regulators of T-cell development, function and ageing [J].
Kroesen, Bart-Jan ;
Teteloshvili, Nato ;
Smigielska-Czepiel, Katarzyna ;
Brouwer, Elisabeth ;
Boots, Anne Mieke H. ;
van den Berg, Anke ;
Kluiver, Joost .
IMMUNOLOGY, 2015, 144 (01) :1-10
[10]   The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes [J].
Marx, Alexander ;
Pfister, Frederick ;
Schalke, Berthold ;
Saruhan-Direskeneli, Guher ;
Melms, Arthur ;
Stroebel, Philipp .
AUTOIMMUNITY REVIEWS, 2013, 12 (09) :875-884