1887

Chapter 99 : Myasthenia Gravis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Myasthenia Gravis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818722/9781555818715_CH99-1.gif /docserver/preview/fulltext/10.1128/9781555818722/9781555818715_CH99-2.gif

Abstract:

Myasthenia gravis (MG) is a disease of striated muscles which clinically manifests as weakness. It is caused by impaired neuromuscular transmission due to a reduction in the number of receptors for the neurotransmitter acetylcholine (ACh) at the postsynaptic myoneural junction. This reduction is caused predominantly by the action of anti-acetylcholine receptor (anti-AChR) antibodies in most instances. The disease occurs with a reported prevalence of 0.5 to 5/100,000 and an incidence of 0.4/100,000/year. MG can occur at any age; however, it typically presents in the second and third decades of life, with a later peak occurring after age 50 (late-onset disease). A female preponderance (3:1 to 4:1) has been reported in the first 40 years of life; thereafter, the incidences are comparable between the sexes.

Citation: Levinson A, Lisak R. 2016. Myasthenia Gravis, p 954-960. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch99
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

The AChR. The subunits of the AChR—α, β, δ, and γ or ε—are arranged like barrel staves around the central ion pore. Each subunit winds through the junctional membrane four times (sites M1, M2, M3, and M4). In the unfolded view of the α subunit, the amino-terminal end of the α subunit is extracellular, where it is accessible to ACh, which binds at the site shown (amino acids 192 and 193). In MG, autoantibodies may bind to various epitopes of all subunits, but a high proportion of antibodies bind to the main immunogenic region of the α subunit.

Citation: Levinson A, Lisak R. 2016. Myasthenia Gravis, p 954-960. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch99
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Schematic representation of the myoneural junction. Vesicles of ACh release their contents at active zones across from AChRs in response to impulses conducted down nerve axons. ACh diffuses across the synaptic cleft and binds to AChRs when not interdicted by AChE, with opening of the ion channel and the generation of endplate potentials. Action potential is propagated to muscle when sufficient amplitude of summated endplate potentials is attained. MuSK is a neuromuscular protein that anchors AChRs to the muscle membrane. LRP4 is a receptor for agrin, which activates clustering of MuSK and AChRs.

Citation: Levinson A, Lisak R. 2016. Myasthenia Gravis, p 954-960. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch99
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818722.ch99
1. Lisak RP, Barchi RL, . 1982. Myasthenia gravis, p 5 36. In Walton JN (ed), Major Problems in Neurology, vol 11. WB Saunders, Philadelphia, PA.
2. Engel AG, Shen XM, Selcen D, Sine S . 2012. New horizons for congenital myasthenic syndromes. Ann N Y Acad Sci 1275 : 54 62.[CrossRef].[PubMed]
3. Watson D, Lisak R, . 1994. Myasthenia gravis: an overview, p 1 20. In Lisak R (ed), Handbook of Myasthenia Gravis and Myasthenic Syndromes. Marcel Dekker, New York, NY.
4. Sanes JR, Apel ED, Gautam M, Glass D, Grady RM, Martin PT, Nichol MC, Yancopoulos GD . 1998. Agrin receptors at the skeletal neuromuscular junction. Ann N Y Acad Sci 841 : 1 13.[PubMed].[CrossRef]
5. Levinson AI, Zweiman B, Lisak RP . 1987. Immunopathogenesis and treatment of myasthenia gravis. J Clin Immunol 7 : 187 197.[PubMed].[CrossRef]
6. Tindall RS . 1981. Humoral immunity in myasthenia gravis: biochemical characterization of acquired antireceptor antibodies and clinical correlations. Ann Neurol 10 : 437 447.[CrossRef].[PubMed]
7. Papadouli I, Sakarellos C, Tzartos SJ . 1993. High-resolution epitope mapping and fine antigenic characterization of the main immunogenic region of the acetylcholine receptor. Improving the binding activity of synthetic analogues of the region. Eur J Biochem 211 : 227 234.[PubMed].[CrossRef]
8. Drachman DB, Adams RN, Josifek LF, Pestronk A, Stanley EF . 1981. Antibody-mediated mechanisms of ACh receptor loss in myasthenia gravis: clinical relevance. Ann N Y Acad Sci 377 : 175 188.[PubMed].[CrossRef]
9. Engel AG, Sahashi K, Fumagalli G . 1981. The immunopathology of acquired myasthenia gravis. Ann N Y Acad Sci 377 : 158 174.[PubMed].[CrossRef]
10. Drachman DB, Angus CW, Adams RN, Michelson JD, Hoffman GJ . 1978. Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation. N Engl J Med 298 : 1116 1122.[CrossRef].[PubMed]
11. Richman DP, Wollmann RL, Maselli RA, Gomez CM, Corey AL, Agius MA, Fairclough RH . 1993. Effector mechanisms of myasthenic antibodies. Ann N Y Acad Sci 681 : 264 273.[PubMed].[CrossRef]
12. Levinson AI . 2013. Modeling the intrathymic pathogenesis of myasthenia gravis. J Neurol Sci 333 : 60 67.[CrossRef].[PubMed]
13. Sanders DB, . 1994. Electrophysiological and pharmacological tests in neuromuscular junction disorders, p 103 148. In Lisak RP (ed), Handbook of Myasthenia Gravis and Myasthenic Syndromes. Marcel Dekker, New York, NY.
14. Leite MI, Waters P, Vincent A . 2010. Diagnostic use of autoantibodies in myasthenia gravis. Autoimmunity 43 : 371 379.[CrossRef].[PubMed]
15. Drachman DB, Adams RN, Josifek LF, Self SG . 1982. Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis. N Engl J Med 307 : 769 775.[CrossRef].[PubMed]
16. Howard FM Jr, Lennon VA, Finley J, Matsumoto J, Elveback LR . 1987. Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci 505 : 526 538.[PubMed].[CrossRef]
17. McKeon A, Lennon VA, Jacob A, Matiello M, Lucchinetti CF, Kale N, Chan KH, Weinshenker BG, Apiwattinakul M, Wingerchuk DM, Pittock SJ . 2009. Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica. Muscle Nerve 39 : 87 90.[CrossRef].[PubMed]
18. Simpson JA . 1966. Myasthenia gravis as an autoimmune disease: clinical aspects. Ann N Y Acad Sci 135 : 506 516.[PubMed].[CrossRef]
19. Lennon VA, Lambert EH, Whittingham S, Fairbanks V . 1982. Autoimmunity in the Lambert-Eaton myasthenic syndrome. Muscle Nerve 5( 9S) : S21 S25.[PubMed]
20. Cikes N, Momoi MY, Williams CL, Howard FM Jr, Hoagland HC, Whittingham S, Lennon VA . 1988. Striational autoantibodies: quantitative detection by enzyme immunoassay in myasthenia gravis, thymoma, and recipients of D-penicillamine or allogeneic bone marrow. Mayo Clin Proc 63 : 474 481.[PubMed].[CrossRef]
21. Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, Beeson D, Willcox N, Vincent A . 2008. IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain 131 : 1940 1952.[CrossRef].[PubMed]
22. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A . 2001. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 7 : 365 368.[CrossRef].[PubMed]
23. McConville J, Farrugia ME, Beeson D, Kishore U, Metcalfe R, Newsom-Davis J, Vincent A . 2004. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 55 : 580 584.[CrossRef].[PubMed]
24. Zhou L, McConville J, Chaudhry V, Adams RN, Skolasky RL, Vincent A, Drachman DB . 2004. Clinical comparison of muscle-specific tyrosine kinase (MuSK) antibody-positive and -negative myasthenic patients. Muscle Nerve 30 : 55 60.[CrossRef].[PubMed]
25. Matthews I, Chen S, Hewer R, McGrath V, Furmaniak J, Rees Smith B . 2004. Muscle-specific receptor tyrosine kinase autoantibodies—a new immunoprecipitation assay. Clin Chim Acta 348 : 95 99.[CrossRef].[PubMed]
26. Farrugia ME, Robson MD, Clover L, Anslow P, Newsom-Davis J, Kennett R, Hilton-Jones D, Matthews PM, Vincent A . 2006. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis. Brain 129 : 1481 1492.[CrossRef].[PubMed]
27. Vincent A, Leite MI . 2005. Neuromuscular junction autoimmune disease: muscle specific kinase antibodies and treatments for myasthenia gravis. Curr Opin Neurol 18 : 519 525.[PubMed].[CrossRef]
28. Sanders DB, El-Salem K, Massey JM, McConville J, Vincent A . 2003. Clinical aspects of MuSK antibody positive seronegative MG. Neurology 60 : 1978 1980.[PubMed].[CrossRef]
29. Cole RN, Reddel SW, Gervásio OL, Phillips WD . 2008. Anti-MuSK patient antibodies disrupt the mouse neuromuscular junction. Ann Neurol 63 : 782 789.[CrossRef].[PubMed]
30. Morsch M, Reddel SW, Ghazanfari N, Toyka KV, Phillips WD . 2012. Muscle specific kinase autoantibodies cause synaptic failure through progressive wastage of postsynaptic acetylcholine receptors. Exp Neurol 237 : 286 295.[CrossRef].[PubMed]
31. Higuchi O, Hamuro J, Motomura M, Yamanashi Y . 2011. Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol 69 : 418 422.[CrossRef].[PubMed]
32. Pevzner A, Schoser B, Peters K, Cosma NC, Karakatsani A, Schalke B, Melms A, Kröger S . 2012. Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis. J Neurol 259 : 427 435.[CrossRef].[PubMed]
33. Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, Xiong WC, Lisak RP, Tzartos SJ, Mei L . 2012. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol 69 : 445 451.[CrossRef].[PubMed]
34. Cossins J, Belaya K, Zoltowska K, Koneczny I, Maxwell S, Jacobson L, Leite MI, Waters P, Vincent A, Beeson D . 2012. The search for new antigenic targets in myasthenia gravis. Ann N Y Acad Sci 1275 : 123 128.[CrossRef].[PubMed]
35. Zhang B, Shen C, Bealmear B, Ragheb S, Xiong W-C, Lewis RA, Lisak RP, Mei L . 2014. Autoantibodies to agrin in myasthenia gravis patients. PLoS One 9 : e91816.[CrossRef].[PubMed]
36. McKeon A, Lennon VA, LaChance DH, Klein CJ, Pittock SJ . 2013. Striational antibodies in a paraneoplastic context. Muscle Nerve 47 : 585 587.[CrossRef].[PubMed]
37. Mygland A, Tysnes OB, Matre R, Volpe P, Aarli JA, Gilhus NE . 1992. Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma. Ann Neurol 32 : 589 591.[CrossRef].[PubMed]
38. Romi F, Skeie GO, Aarli JA, Gilhus NE . 2000. The severity of myasthenia gravis correlates with the serum concentration of titin and ryanodine receptor antibodies. Arch Neurol 57 : 1596 1600.[PubMed]
39. Skeie GO, Mygland A, Aarli JA, Gilhus NE . 1995. Titin antibodies in patients with late onset myasthenia gravis: clinical correlations. Autoimmunity 20 : 99 104.[PubMed].[CrossRef]
40. Aarli JA . 2008. Myasthenia gravis in the elderly: is it different? Ann N Y Acad Sci 1132 : 238 243.[CrossRef].[PubMed]
41. Strauss AJ . 1968. Myasthenia gravis, autoimmunity and the thymus. Adv Intern Med 14 : 241 280.[PubMed]
42. Vernino S, Lennon VA . 2004. Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res 10 : 7270 7275.[CrossRef].[PubMed]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error