Advances in autoimmune myasthenia gravis management

被引:44
作者
Wang, Shuhui [1 ,2 ]
Breskovska, Iva [1 ]
Gandhy, Shreya [1 ]
Punga, Anna Rostedt [3 ]
Guptill, Jeffery T. [4 ]
Kaminski, Henry J. [1 ]
机构
[1] George Washington Univ, Dept Neurol, Washington, DC USA
[2] Capital Med Univ, Beijing Friendship Hosp, Dept Neurol, Beijing, Peoples R China
[3] Uppsala Univ, Clin Neurophysiol, Dept Neurosci, Uppsala, Sweden
[4] Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
Myasthenia gravis; clinical trials; mycophenolate; tacrolimus; prednisone; eculizumab; rituximab; interleukins; plasma cells; acetylcholine receptor antibody; muscle-specific kinase; ANTIACETYLCHOLINE RECEPTOR ANTIBODIES; SINGLE-FIBER ELECTROMYOGRAPHY; COLONY-STIMULATING FACTOR; NEONATAL FC-RECEPTOR; T-CELL REPERTOIRE; MYCOPHENOLATE-MOFETIL; ACETYLCHOLINE-RECEPTOR; B-CELLS; DOUBLE-BLIND; PLASMA-CELLS;
D O I
10.1080/14737175.2018.1491310
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies. Areas covered: Clinical presentation and pathology vary considerably among patients with some having weakness limited to the ocular muscles and others having profound generalized weakness leading to respiratory insufficiency. MG is an antibody-mediated disorder dependent on autoreactive B cells which require T-cell support. Treatments focus on elimination of circulating autoantibodies or inhibition of effector mechanisms by a broad spectrum of approaches from plasmapheresis to B-cell elimination to complement inhibition. Expert commentary: Standard therapies and those under development are disease modifying and not curative. As a rare disease, clinical trials are challenged in patient recruitment. The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.
引用
收藏
页码:573 / 588
页数:16
相关论文
共 230 条
[1]   Ablation of IL-17 expression moderates experimental autoimmune myasthenia gravis disease severity [J].
Aguilo-Seara, Gabriela ;
Xie, Yanchen ;
Sheehan, Jarrod ;
Kusner, Linda L. ;
Kaminski, Henry J. .
CYTOKINE, 2017, 96 :279-285
[2]   Intravenous immunoglobulin as treatment for myasthenia gravis: current evidence and outcomes [J].
Alabdali, Majed ;
Barnett, Carolina ;
Katzberg, Hans ;
Breiner, Ari ;
Bril, Vera .
EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2014, 10 (12) :1659-1665
[3]   The role of T regulatory cells in immunopathogenesis of myasthenia gravis: implications for therapeutics [J].
Alahgholi-Hajibehzad, Mahdi ;
Kasapoglu, Pinar ;
Jafari, Reza ;
Rezaei, Nima .
EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2015, 11 (07) :859-870
[4]   Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity [J].
Alahgholi-Hajibehzad, Mandi ;
Oflazer, Piraye ;
Aysal, Fikret ;
Durmus, Hacer ;
Gulsen-Parman, Yesim ;
Marx, Alexander ;
Deymeer, Feza ;
Saruhan-Direskeneli, Guher .
JOURNAL OF NEUROIMMUNOLOGY, 2015, 281 :51-60
[5]   Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals [J].
Alshekhlee, A. ;
Miles, J. D. ;
Katirji, B. ;
Preston, D. C. ;
Kaminski, H. J. .
NEUROLOGY, 2009, 72 (18) :1548-1554
[6]   Projection of an immunological self shadow within the thymus by the aire protein [J].
Anderson, MS ;
Venanzi, ES ;
Klein, L ;
Chen, ZB ;
Berzins, SP ;
Turley, SJ ;
von Boehmer, H ;
Bronson, R ;
Dierich, A ;
Benoist, C ;
Mathis, D .
SCIENCE, 2002, 298 (5597) :1395-1401
[7]   PROTEIN-A IMMUNOADSORPTION IN IMMUNOSUPPRESSION-RESISTANT MYASTHENIA-GRAVIS [J].
ANTOZZI, C ;
BERTA, E ;
CONFALONIERI, P ;
ZUFFI, M ;
CORNELIO, F ;
MANTEGAZZA, R .
LANCET, 1994, 343 (8889) :124-124
[8]   PREVENTION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS BY MANIPULATION OF THE IMMUNE NETWORK WITH A COMPLEMENTARY PEPTIDE FOR THE ACETYLCHOLINE-RECEPTOR [J].
ARAGA, S ;
LEBOEUF, RD ;
BLALOCK, JE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (18) :8747-8751
[9]  
Araga S, 1994, Immunomethods, V5, P130, DOI 10.1006/immu.1994.1047
[10]   A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help [J].
Araga, S ;
Xu, LK ;
Nakashima, K ;
Villain, M ;
Blalock, JE .
FASEB JOURNAL, 2000, 14 (01) :185-196