327
Views
111
CrossRef citations to date
0
Altmetric
Review

Muscle autoantibodies in myasthenia gravis: beyond diagnosis?

&
Pages 427-438 | Published online: 10 Jan 2014

References

  • Phillips LH 2nd. The epidemiology of myasthenia gravis. Ann. NY Acad. Sci. 998, 407–412 (2003).
  • Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 8(5), 475–490 (2009).
  • Drachman DB. Myasthenia gravis. N. Engl. J. Med. 330(25), 1797–1810 (1994).
  • Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science 180(4088), 871–872 (1973).
  • Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat. Med. 7(3), 365–368 (2001).
  • McConville J, Farrugia ME, Beeson D et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann. Neurol. 55(4), 580–584 (2004).
  • Leite MI, Jacob S, Viegas S et al. IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain 131(Pt 7), 1940–1952 (2008).
  • Romi F, Skeie GO, Aarli JA, Gilhus NE. Muscle autoantibodies in subgroups of myasthenia gravis patients. J. Neurol. 247(5), 369–375 (2000).
  • Drachman DB, Adams RN, Stanley EF, Pestronk A. Mechanisms of acetylcholine receptor loss in myasthenia gravis. J. Neurol. Neurosurg. Psychiatr. 43(7), 601–610 (1980).
  • Toyka KV, Drachman DB, Griffin DE et al. Myasthenia gravis. Study of humoral immune mechanisms by passive transfer to mice. N. Engl. J. Med. 296(3), 125–131 (1977).
  • Lefvert AK. Immunoglobulins in myasthenia gravis. Kinetic properties of the acetylcholine-receptor antibody studied during lymph drainage. Clin. Exp. Immunol. 34(1), 111–117 (1978).
  • Newsom-Davis J, Pinching AJ, Vincent A, Wilson SG. Function of circulating antibody to acetylcholine receptor in myasthenia gravis: investigation by plasma exchange. Neurology 28(3), 266–272 (1978).
  • Lindstrom J. An assay for antibodies to human acetylcholine receptor in serum from patients with myasthenia gravis. Clin. Immunol. Immunopathol. 7(1), 36–43 (1977).
  • Tzartos SJ, Lindstrom JM. Monoclonal antibodies used to probe acetylcholine receptor structure: localization of the main immunogenic region and detection of similarities between subunits. Proc. Natl Acad. Sci. USA 77(2), 755–759 (1980).
  • Gomez AM, Van Den Broeck J, Vrolix K et al. Antibody effector mechanisms in myasthenia gravis-pathogenesis at the neuromuscular junction. Autoimmunity 43(5–6), 353–370 (2010).
  • Willcox N, Leite MI, Kadota Y et al. Autoimmunizing mechanisms in thymoma and thymus. Ann. NY Acad. Sci. 1132, 163–173 (2008).
  • Schluep M, Willcox N, Vincent A, Dhoot GK, Newsom-Davis J. Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study. Ann. Neurol. 22(2), 212–222 (1987).
  • Morgenthaler TI, Brown LR, Colby TV, Harper CM Jr, Coles DT. Thymoma. Mayo Clin. Proc. 68(11), 1110–1123 (1993).
  • Aarli J. Myasthenia gravis and thymoma. In: Handbook of Myasthenia Gravis and Myasthenic Syndromes. Lisak RP (Ed.). Marcel Dekker, Inc., NY, USA, 207–224.
  • Heidenreich F, Vincent A, Willcox N, Newsom-Davis J. Anti-acetylcholine receptor antibody specificities in serum and in thymic cell culture supernatants from myasthenia gravis patients. Neurology 38(11), 1784–1788 (1988).
  • Gilhus NE, Aarli JA, Matre R. Myasthenia gravis: the specificities of skeletal muscle and thymus antibodies. Acta Neurol. Scand. 68(5), 328–336 (1983).
  • Hohlfeld R, Kalies I, Kohleisen B, Heininger K, Conti-Tronconi B, Toyka KV. Myasthenia gravis: stimulation of antireceptor autoantibodies by autoreactive T cell lines. Neurology 36(5), 618–621 (1986).
  • Melms A, Schalke BC, Kirchner T, Müller-Hermelink HK, Albert E, Wekerle H. Thymus in myasthenia gravis. Isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients. J. Clin. Invest. 81(3), 902–908 (1988).
  • Sommer N, Willcox N, Harcourt GC, Newsom-Davis J. Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. Ann. Neurol. 28(3), 312–319 (1990).
  • Sommer N, Harcourt GC, Willcox N, Beeson D, Newsom-Davis J. Acetylcholine receptor-reactive T lymphocytes from healthy subjects and myasthenia gravis patients. Neurology 41(8), 1270–1276 (1991).
  • Mygland A, Vincent A, Newsom-Davis J et al. Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia. Arch. Neurol. 57(4), 527–531 (2000).
  • Kadota Y, Okumura M, Miyoshi S et al. Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-gamma). Clin. Exp. Immunol. 121(1), 59–68 (2000).
  • Scarpino S, Di Napoli A, Stoppacciaro A et al. Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas. Clin. Exp. Immunol. 149(3), 504–512 (2007).
  • Ströbel P, Rosenwald A, Beyersdorf N et al. Selective loss of regulatory T cells in thymomas. Ann. Neurol. 56(6), 901–904 (2004).
  • Howard FM Jr, Lennon VA, Finley J, Matsumoto J, Elveback LR. Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann. NY Acad. Sci. 505, 526–538 (1987).
  • Lindstrom J. An assay for antibodies to human acetylcholine receptor in serum from patients with myasthenia gravis. Clin. Immunol. Immunopathol. 7(1), 36–43 (1977).
  • Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 26(11), 1054–1059 (1976).
  • Lefvert AK, Bergström K, Matell G, Osterman PO, Pirskanen R. Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications. J. Neurol. Neurosurg. Psychiatr. 41(5), 394–403 (1978).
  • Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J. Neurol. Neurosurg. Psychiatr. 48(12), 1246–1252 (1985).
  • Agius MA, Richman DP, Vincent A. Autoantibody testing in the diagnosis and management of autoimmune disorders of neuromuscular transmission and related disorders. In: Myasthenia Gravis and Related Disorders (2nd Edition). Kaminski HJ (Ed.). Humana Press, NJ, USA, 143–156 (2009).
  • Vincent A, Newsom-Davis J. Acetylcholine receptor antibody characteristics in myasthenia gravis. I. Patients with generalized myasthenia or disease restricted to ocular muscles. Clin. Exp. Immunol. 49(2), 257–265 (1982).
  • Lefvert AK, Björkholm M. Antibodies against the acetylcholine receptor in hematologic disorders: implications for the development of myasthenia gravis after bone marrow grafting. N. Engl. J. Med. 317(3), 170 (1987).
  • Lennon VA. Serological diagnosis of myasthenia gravis and Lambert–Eaton myasthenic syndrome. In: Handbook of Myasthenia Gravis and Myasthenic Syndromes. Lisak RP (Ed.). Marcel Dekker, NY, USA, 149–164 (1994).
  • McKeon A, Lennon VA, Jacob A et al. Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica. Muscle Nerve 39(1), 87–90 (2009).
  • Chan KH, Lachance DH, Harper CM, Lennon VA. Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve 36(5), 651–658 (2007).
  • Vernino S, Lennon VA. Autoantibody profiles and neurological correlations of thymoma. Clin. Cancer Res. 10(21), 7270–7275 (2004).
  • Tindall RS. Humoral immunity in myasthenia gravis: biochemical characterization of acquired antireceptor antibodies and clinical correlations. Ann. Neurol. 10(5), 437–447 (1981).
  • Jaretzki A 3rd, Barohn RJ, Ernstoff RM et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 55(1), 16–23 (2000).
  • Besinger UA, Toyka KV, Hömberg M, Heininger K, Hohlfeld R, Fateh-Moghadam A. Myasthenia gravis: long-term correlation of binding and bungarotoxin blocking antibodies against acetylcholine receptors with changes in disease severity. Neurology 33(10), 1316–1321 (1983).
  • Oosterhuis HJ, Limburg PC, Hummel-Tappel E, The TH. Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 2. Clinical and serological follow-up of individual patients. J. Neurol. Sci. 58(3), 371–385 (1983).
  • Oosterhuis HJ, Limburg PC, Hummel-Tappel E, Van den Burg W, The TH. Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 3. The effect of thymectomy. J. Neurol. Sci. 69(3), 335–343 (1985).
  • Tindall RS. Humoral immunity in myasthenia gravis: effect of steroids and thymectomy. Neurology 30(5), 554–557 (1980).
  • Vincent A, Newsom-Davis J, Newton P, Beck N. Acetylcholine receptor antibody and clinical response to thymectomy in myasthenia gravis. Neurology 33(10), 1276–1282 (1983).
  • Zong Y, Zhang B, Gu S et al. Structural basis of agrin-LRP4-MuSK signaling. Genes Dev. 26(3), 247–258 (2012).
  • Punga AR, Lin S, Oliveri F, Meinen S, Rüegg MA. Muscle-selective synaptic disassembly and reorganization in MuSK antibody positive MG mice. Exp. Neurol. 230(2), 207–217 (2011).
  • Shiraishi H, Motomura M, Yoshimura T et al. Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis. Ann. Neurol. 57(2), 289–293 (2005).
  • Cole RN, Reddel SW, Gervásio OL, Phillips WD. Anti-MuSK patient antibodies disrupt the mouse neuromuscular junction. Ann. Neurol. 63(6), 782–789 (2008).
  • Shigemoto K, Kubo S, Maruyama N et al. Induction of myasthenia by immunization against muscle-specific kinase. J. Clin. Invest. 116(4), 1016–1024 (2006).
  • Jha S, Xu K, Maruta T et al. Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK). J. Neuroimmunol. 175(1–2), 107–117 (2006).
  • ter Beek WP, Martínez-Martínez P, Losen M et al. The effect of plasma from muscle-specific tyrosine kinase myasthenia patients on regenerating endplates. Am. J. Pathol. 175(4), 1536–1544 (2009).
  • Lavrnic D, Losen M, Vujic A et al. The features of myasthenia gravis with autoantibodies to MuSK. J. Neurol. Neurosurg. Psychiatr. 76(8), 1099–1102 (2005).
  • Mori S, Kubo S, Akiyoshi T et al. Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis. Am. J. Pathol. 180(2), 798–810 (2012).
  • Mori S, Yamada S, Kubo S et al. Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanisms in a rabbit model of myasthenia gravis. J. Neuroimmunol. 244(1–2), 1–7 (2012).
  • Klooster R, Plomp JJ, Huijbers MG et al. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice. Brain 135(Pt 4), 1081–1101 (2012).
  • Kawakami Y, Ito M, Hirayama M et al. Anti-MuSK autoantibodies block binding of collagen Q to MuSK. Neurology 77(20), 1819–1826 (2011).
  • Hatanaka Y, Hemmi S, Morgan MB et al. Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody-positive MG. Neurology 65(9), 1508–1509 (2005).
  • Zhu D, Yang Z, Luo Z, Luo S, Xiong WC, Mei L. Muscle-specific receptor tyrosine kinase endocytosis in acetylcholine receptor clustering in response to agrin. J. Neurosci. 28(7), 1688–1696 (2008).
  • Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve 44(1), 36–40 (2011).
  • Evoli A, Tonali PA, Padua L et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 126(Pt 10), 2304–2311 (2003).
  • Ohta K, Shigemoto K, Kubo S et al. MuSK antibodies in AChR Ab-seropositive MG vs AChR Ab-seronegative MG. Neurology 62(11), 2132–2133 (2004).
  • Sanders DB, El-Salem K, Massey JM, McConville J, Vincent A. Clinical aspects of MuSK antibody positive seronegative MG. Neurology 60(12), 1978–1980 (2003).
  • Suzuki S, Utsugisawa K, Nagane Y, Satoh T, Kuwana M, Suzuki N. Clinical and immunological differences between early and late-onset myasthenia gravis in Japan. J. Neuroimmunol. 230(1–2), 148–152 (2011).
  • Sanders DB, Juel VC. MuSK-antibody positive myasthenia gravis: questions from the clinic. J. Neuroimmunol. 201–202, 85–89 (2008).
  • Leite MI, Ströbel P, Jones M et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann. Neurol. 57(3), 444–448 (2005).
  • Bartoccioni E, Scuderi F, Minicuci GM, Marino M, Ciaraffa F, Evoli A. Anti-MuSK antibodies: correlation with myasthenia gravis severity. Neurology 67(3), 505–507 (2006).
  • Niks EH, van Leeuwen Y, Leite MI et al. Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1. J. Neuroimmunol. 195(1–2), 151–156 (2008).
  • Strauss AJ, Kemp PG Jr. Serum autoantibodies in myasthenia gravis and thymoma: selective affinity for I-bands of striated muscle as a guide to identification of antigen(s). J. Immunol. 99(5), 945–953 (1967).
  • Marx A, Willcox N, Leite MI et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 43(5–6), 413–427 (2010).
  • Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. Eur. J. Neurol. 9(1), 55–61 (2002).
  • Wang K, McClure J, Tu A. Titin: major myofibrillar components of striated muscle. Proc. Natl Acad. Sci. USA 76(8), 3698–3702 (1979).
  • Yamamoto AM, Gajdos P, Eymard B et al. Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients. Arch. Neurol. 58(6), 885–890 (2001).
  • Romi F, Skeie GO, Aarli JA, Gilhus NE. The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptor antibodies. Arch. Neurol. 57(11), 1596–1600 (2000).
  • Skeie GO, Mygland A, Aarli JA, Gilhus NE. Titin antibodies in patients with late onset myasthenia gravis: clinical correlations. Autoimmunity 20(2), 99–104 (1995).
  • Romi F, Skeie GO, Vedeler C, Aarli JA, Zorzato F, Gilhus NE. Complement activation by titin and ryanodine receptor autoantibodies in myasthenia gravis. A study of IgG subclasses and clinical correlations. J. Neuroimmunol. 111(1–2), 169–176 (2000).
  • Skeie GO, Aarli JA, Matre R et al. Titin antibody positive myasthenia gravis patients have a cellular immune response against the main immunogenic region of titin. Eur. J. Neurol. 4, 131–137 (1997).
  • Romi F, Bø L, Skeie GO, Myking A, Aarli JA, Gilhus NE. Titin and ryanodine receptor epitopes are expressed in cortical thymoma along with costimulatory molecules. J. Neuroimmunol. 128(1–2), 82–89 (2002).
  • Skeie GO, Freiburg A, Kolmerer B et al. Titin transcripts in thymomas. J. Autoimmun. 10(6), 551–557 (1997).
  • Coronado R, Morrissette J, Sukhareva M, Vaughan DM. Structure and function of ryanodine receptors. Am. J. Physiol. 266(6 Pt 1), C1485–C1504 (1994).
  • Mygland A, Aarli JA, Matre R, Gilhus NE. Ryanodine receptor antibodies related to severity of thymoma associated myasthenia gravis. J. Neurol. Neurosurg. Psychiatr. 57(7), 843–846 (1994).
  • Romi F, Aarli JA, Gilhus NE. Myasthenia gravis patients with ryanodine receptor antibodies have distinctive clinical features. Eur. J. Neurol. 14(6), 617–620 (2007).
  • Mygland A, Tysnes OB, Aarli JA, Matre R, Gilhus NE. IgG subclass distribution of ryanodine receptor autoantibodies in patients with myasthenia gravis and thymoma. J. Autoimmun. 6(4), 507–515 (1993).
  • Skeie GO, Mygland A, Treves S, Gilhus NE, Aarli JA, Zorzato F. Ryanodine receptor antibodies in myasthenia gravis: epitope mapping and effect on calcium release in vitro. Muscle Nerve 27(1), 81–89 (2003).
  • Mygland A, Tysnes OB, Matre R, Aarli JA, Gilhus NE. Anti-cardiac ryanodine receptor antibodies in thymoma-associated myasthenia gravis. Autoimmunity 17(4), 327–331 (1994).
  • Skeie GO, Lunde PK, Sejersted OM, Mygland A, Aarli JA, Gilhus NE. Myasthenia gravis sera containing antiryanodine receptor antibodies inhibit binding of [3H]-ryanodine to sarcoplasmic reticulum. Muscle Nerve 21(3), 329–335 (1998).
  • Ohta M, Ohta K, Itoh N, Kurobe M, Hayashi K, Nishitani H. Anti-skeletal muscle antibodies in the sera from myasthenic patients with thymoma: identification of anti-myosin, actomyosin, actin, and alpha-actinin antibodies by a solid-phase radioimmunoassay and a western blotting analysis. Clin. Chim. Acta 187(3), 255–264 (1990).
  • Yamamoto T, Sato T, Sugita H. Antifilamin, antivinculin, and antitropomyosin antibodies in myasthenia gravis. Neurology 37(8), 1329–1333 (1987).
  • Skeie GO, Romi F. Paraneoplastic myasthenia gravis: immunological and clinical aspects. Eur. J. Neurol. 15(10), 1029–1033 (2008).
  • Suzuki S, Utsugisawa K, Yoshikawa H et al. Autoimmune targets of heart and skeletal muscles in myasthenia gravis. Arch. Neurol. 66(11), 1334–1338 (2009).
  • Suzuki S, Utsugisawa K, Nagane Y, Suzuki N. Three types of striational antibodies in myasthenia gravis. Autoimmune Dis. 2011, 740583 (2011).
  • Suzuki S, Satoh T, Yasuoka H et al. Novel autoantibodies to a voltage-gated potassium channel Kv1.4 in a severe form of myasthenia gravis. J. Neuroimmunol. 170(1–2), 141–149 (2005).
  • Romi F, Suzuki S, Suzuki N, Petzold A, Plant GT, Gilhus NE. Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis. J. Neurol. 259(7), 1312–1316 (2011).
  • Agius MA, Zhu S, Kirvan CA et al. Rapsyn antibodies in myasthenia gravis. Ann. NY Acad. Sci. 841, 516–521 (1998).
  • Agius MA, Zhu S, Aarli JA. Antirapsyn antibodies occur commonly in patients with lupus. Ann. NY Acad. Sci. 841, 525–526 (1998).
  • Phillips TM, Manz HJ, Smith FA, Jaffe HA, Cohan SL. The detection of anti-cholinesterase antibodies in myasthenia gravis. Ann. NY Acad. Sci. 377, 360–371 (1981).
  • Geen J, Howells RC, Ludgate M, Hullin DA, Hogg SI. The prevalence of anti-acetylcholinesterase antibodies in autoimmune disease. Autoimmunity 37(8), 579–585 (2004).
  • Higuchi O, Hamuro J, Motomura M, Yamanashi Y. Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann. Neurol. 69(2), 418–422 (2011).
  • Pevzner A, Schoser B, Peters K et al. Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis. J. Neurol. 259(3), 427–435 (2012).
  • Zhang B, Tzartos JS, Belimezi M et al. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch. Neurol. 69(4), 445–451 (2012).
  • Yang L, Maxwell S, Leite MI et al. Non-radioactive serological diagnosis of myasthenia gravis and clinical features of patients from Tianjin, China. J. Neurol. Sci. 301(1–2), 71–76 (2011).
  • Papp K, Prechl J. The use of antigen microarrays in antibody profiling. Methods Mol. Biol. 815, 175–185 (2012).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.