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{{Myasthenia gravis}} | {{Myasthenia gravis}} | ||
==Overview== | ==Overview== | ||
Myasthenia gravis may be classified into 4 sub types based on presence of [[autoantibodies]]: Pure ocular form, generalized form with anti-AChR antibodies, the forms without classical anti-AChR antibodies, neonatal MG, congenital. | |||
==Classification== | |||
== | Myasthenia gravis may be classified into 4 sub types based on presence of [[autoantibodies]]. | ||
* | ==== Pure ocular form ==== | ||
* | * [[Ocular]] [[Symptom|symptoms]] are the initial [[symptom]] in most of the [[Myasthenia gravis|MG]] cases. | ||
* In about 15 percent of these patients this initial [[symptom]] will not progress to generalized disease after 2 years and they will classify as pure [[ocular]] form of the Myasthenia gravis. | |||
* | * In approximately 50 percent of these patients we can’t detect [[antibodies]] by classical assay and we need to detect them through cell-based assay.<ref name="pmid18515870">{{cite journal |vauthors=Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, Beeson D, Willcox N, Vincent A |title=IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis |journal=Brain |volume=131 |issue=Pt 7 |pages=1940–52 |date=July 2008 |pmid=18515870 |pmc=2442426 |doi=10.1093/brain/awn092 |url=}}</ref> | ||
* | |||
* | ==== Generalized form with anti-AChR antibodies ==== | ||
* | About 85 percent of [[Myasthenia gravis|MG]] patients develop generalized disease with [[autoantibody]] against AchR.<ref name="pmid4087000">{{cite journal |vauthors=Vincent A, Newsom-Davis J |title=Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays |journal=J. Neurol. Neurosurg. Psychiatry |volume=48 |issue=12 |pages=1246–52 |date=December 1985 |pmid=4087000 |pmc=1028609 |doi= |url=}}</ref> These [[antibodies]] are IgG1 and IgG3 subclasses which can bind to [[complement]].<ref name="pmid23535160">{{cite journal |vauthors=Verschuuren JJ, Huijbers MG, Plomp JJ, Niks EH, Molenaar PC, Martinez-Martinez P, Gomez AM, De Baets MH, Losen M |title=Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4 |journal=Autoimmun Rev |volume=12 |issue=9 |pages=918–23 |date=July 2013 |pmid=23535160 |doi=10.1016/j.autrev.2013.03.001 |url=}}</ref> [[Thymus|Thymic]] abnormalities are more common in this group, especially thymic follicular hyperplasia.<ref name="pmid6228745">{{cite journal |vauthors=Berrih S, Morel E, Gaud C, Raimond F, Le Brigand H, Bach JF |title=Anti-AChR antibodies, thymic histology, and T cell subsets in myasthenia gravis |journal=Neurology |volume=34 |issue=1 |pages=66–71 |date=January 1984 |pmid=6228745 |doi= |url=}}</ref> this subtype can be further divided into 2 groups: | ||
* | * Early onset myasthenia gravis (onset of the disease before the age of 50 (EOMG)): In this group we have [[female]] predominance with the ratio of 3/1. Thymic follicular [[hyperplasia]] is more common in this group and is believed to be related to deregulation of [[sex hormones]] and their receptors on [[Thymus|thymic]] cells.<ref name="pmid7676132">{{cite journal |vauthors=Eymard B, Berrih-Aknin S |title=[Role of the thymus in the physiopathology of myasthenia] |language=French |journal=Rev. Neurol. (Paris) |volume=151 |issue=1 |pages=6–15 |date=January 1995 |pmid=7676132 |doi= |url=}}</ref><ref name="pmid15661863">{{cite journal |vauthors=Nancy P, Berrih-Aknin S |title=Differential estrogen receptor expression in autoimmune myasthenia gravis |journal=Endocrinology |volume=146 |issue=5 |pages=2345–53 |date=May 2005 |pmid=15661863 |pmc=1839841 |doi=10.1210/en.2004-1003 |url=}}</ref> | ||
*These patients can have other [[Autoimmune disease|autoimmune diseases]] like [[Hashimoto's thyroiditis|Hashimoto’s]] disease.<ref name="pmid23792059">{{cite journal |vauthors=Klein R, Marx A, Ströbel P, Schalke B, Nix W, Willcox N |title=Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis |journal=Hum. Immunol. |volume=74 |issue=9 |pages=1184–93 |date=September 2013 |pmid=23792059 |doi=10.1016/j.humimm.2013.06.020 |url=}}</ref> | |||
* Late onset myasthenia gravis (onset of the disease after the age of 50 (LOMG)): Patients with this type of the disease can present with [[thymoma]], a tumor of thymic [[epithelial cells]].<ref name="pmid23535159">{{cite journal |vauthors=Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P |title=The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes |journal=Autoimmun Rev |volume=12 |issue=9 |pages=875–84 |date=July 2013 |pmid=23535159 |doi=10.1016/j.autrev.2013.03.007 |url=}}</ref> In almost 50 percent of them we can find other antibodies like anti-ryanodine antibody, anti-titin antibody and anti-[[striated muscle]] antibody.<ref name="pmid21785709">{{cite journal |vauthors=Suzuki S, Utsugisawa K, Nagane Y, Suzuki N |title=Three types of striational antibodies in myasthenia gravis |journal=Autoimmune Dis |volume=2011 |issue= |pages=740583 |date=2011 |pmid=21785709 |pmc=3139883 |doi=10.4061/2011/740583 |url=}}</ref> most of the patients in this group have severe [[Symptom|symptoms]] like [[bulbar]] involvement.<ref name="pmid17539937">{{cite journal |vauthors=Romi F, Aarli JA, Gilhus NE |title=Myasthenia gravis patients with ryanodine receptor antibodies have distinctive clinical features |journal=Eur. J. Neurol. |volume=14 |issue=6 |pages=617–20 |date=June 2007 |pmid=17539937 |doi=10.1111/j.1468-1331.2007.01785.x |url=}}</ref> | |||
==== The forms without classical anti-AChR antibodies ==== | |||
This subtype can be further divided into 3 groups | |||
* The form with anti-anti-MuSK antibodies: About 5 percent of [[Myasthenia gravis|MG]] patients, especially [[females]] has this [[antibody]] which belongs to IgG4 subclasses and cannot bind to [[complement]].<ref name="pmid12821509">{{cite journal |vauthors=Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E |title=Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis |journal=Brain |volume=126 |issue=Pt 10 |pages=2304–11 |date=October 2003 |pmid=12821509 |doi=10.1093/brain/awg223 |url=}}</ref><ref name="pmid15048899">{{cite journal |vauthors=McConville J, Farrugia ME, Beeson D, Kishore U, Metcalfe R, Newsom-Davis J, Vincent A |title=Detection and characterization of MuSK antibodies in seronegative myasthenia gravis |journal=Ann. Neurol. |volume=55 |issue=4 |pages=580–4 |date=April 2004 |pmid=15048899 |doi=10.1002/ana.20061 |url=}}</ref> their [[symptoms]] are mostly sever and involves [[facial]], [[bulbar]] and [[respiratory]] [[muscles]] but spares [[ocular]] and [[Thymus|thymic]] abnormalities.<ref name="pmid12821509">{{cite journal |vauthors=Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E |title=Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis |journal=Brain |volume=126 |issue=Pt 10 |pages=2304–11 |date=October 2003 |pmid=12821509 |doi=10.1093/brain/awg223 |url=}}</ref><ref name="pmid15732104">{{cite journal |vauthors=Leite MI, Ströbel P, Jones M, Micklem K, Moritz R, Gold R, Niks EH, Berrih-Aknin S, Scaravilli F, Canelhas A, Marx A, Newsom-Davis J, Willcox N, Vincent A |title=Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG |journal=Ann. Neurol. |volume=57 |issue=3 |pages=444–8 |date=March 2005 |pmid=15732104 |doi=10.1002/ana.20386 |url=}}</ref> In these patients both [[presynaptic]] and [[postsynaptic]] components of [[Neuromuscular junction|NMJ]] are affected and the severity of the disease is related to the amount of [[antibodies]].<ref name="pmid23995274">{{cite journal |vauthors=Le Panse R, Berrih-Aknin S |title=Autoimmune myasthenia gravis: autoantibody mechanisms and new developments on immune regulation |journal=Curr. Opin. Neurol. |volume=26 |issue=5 |pages=569–76 |date=October 2013 |pmid=23995274 |doi=10.1097/WCO.0b013e328364d6cd |url=}}</ref><ref name="pmid16894117">{{cite journal |vauthors=Bartoccioni E, Scuderi F, Minicuci GM, Marino M, Ciaraffa F, Evoli A |title=Anti-MuSK antibodies: correlation with myasthenia gravis severity |journal=Neurology |volume=67 |issue=3 |pages=505–7 |date=August 2006 |pmid=16894117 |doi=10.1212/01.wnl.0000228225.23349.5d |url=}}</ref> | |||
* The form with anti-LRP4 antibodies: About 12-50 percent of patients who seems to be [[seronegative]] for anti-AchR and MuSK, presents antibody against LRP4.<ref name="pmid21387385">{{cite journal |vauthors=Higuchi O, Hamuro J, Motomura M, Yamanashi Y |title=Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis |journal=Ann. Neurol. |volume=69 |issue=2 |pages=418–22 |date=February 2011 |pmid=21387385 |doi=10.1002/ana.22312 |url=}}</ref><ref name="pmid21814823">{{cite journal |vauthors=Pevzner A, Schoser B, Peters K, Cosma NC, Karakatsani A, Schalke B, Melms A, Kröger S |title=Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis |journal=J. Neurol. |volume=259 |issue=3 |pages=427–35 |date=March 2012 |pmid=21814823 |doi=10.1007/s00415-011-6194-7 |url=}}</ref><ref name="pmid22158716">{{cite journal |vauthors=Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, Xiong WC, Lisak RP, Tzartos SJ, Mei L |title=Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis |journal=Arch. Neurol. |volume=69 |issue=4 |pages=445–51 |date=April 2012 |pmid=22158716 |doi=10.1001/archneurol.2011.2393 |url=}}</ref> | |||
* The form with clustered AChR antibodies: 5 percent of patients with [[Myasthenia gravis|MG]] doesn’t have any [[antibodies]] but in 50 percent of them we can see clustered AchR with cell assay detection.<ref name="pmid18515870">{{cite journal |vauthors=Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, Beeson D, Willcox N, Vincent A |title=IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis |journal=Brain |volume=131 |issue=Pt 7 |pages=1940–52 |date=July 2008 |pmid=18515870 |pmc=2442426 |doi=10.1093/brain/awn092 |url=}}</ref> | |||
==== Neonatal MG ==== | |||
* 10-20 percent of mothers with [[Myasthenia gravis|MG]] may have infants who display a transient neonatal myasthenia (TNM) for few days to 3 months. | |||
* The cause of this condition is passive transfer of [[antibodies]] to the neonate.<ref name="pmid18434154">{{cite journal |vauthors=Béhin A, Mayer M, Kassis-Makhoul B, Jugie M, Espil-Taris C, Ferrer X, Chatenoud L, Laforêt P, Eymard B |title=Severe neonatal myasthenia due to maternal anti-MuSK antibodies |journal=Neuromuscul. Disord. |volume=18 |issue=6 |pages=443–6 |date=June 2008 |pmid=18434154 |doi=10.1016/j.nmd.2008.03.006 |url=}}</ref> | |||
==== Congenital ==== | |||
* [[Congenital]] form of [[Myasthenia gravis|MG]] follows the [[Mendelian]] pattern and is caused by an error in the [[Gene|genes]] which are expressed in the [[Neuromuscular junction|NMJ]].<ref name="pmid15907919">{{cite journal |vauthors=Engel AG, Sine SM |title=Current understanding of congenital myasthenic syndromes |journal=Curr Opin Pharmacol |volume=5 |issue=3 |pages=308–21 |date=June 2005 |pmid=15907919 |doi=10.1016/j.coph.2004.12.007 |url=}}</ref> | |||
==References== | |||
{{Reflist|2}} | |||
[[Category:Disease]] | |||
[[Category:Autoimmune diseases]] | |||
[[Category:Neurology]] | |||
[[Category:Rheumatology]] | |||
{{WH}} | |||
{{WS}} | |||
<references /> | |||
Latest revision as of 14:11, 15 August 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2]
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Overview
Myasthenia gravis may be classified into 4 sub types based on presence of autoantibodies: Pure ocular form, generalized form with anti-AChR antibodies, the forms without classical anti-AChR antibodies, neonatal MG, congenital.
Classification
Myasthenia gravis may be classified into 4 sub types based on presence of autoantibodies.
Pure ocular form
- Ocular symptoms are the initial symptom in most of the MG cases.
- In about 15 percent of these patients this initial symptom will not progress to generalized disease after 2 years and they will classify as pure ocular form of the Myasthenia gravis.
- In approximately 50 percent of these patients we can’t detect antibodies by classical assay and we need to detect them through cell-based assay.[1]
Generalized form with anti-AChR antibodies
About 85 percent of MG patients develop generalized disease with autoantibody against AchR.[2] These antibodies are IgG1 and IgG3 subclasses which can bind to complement.[3] Thymic abnormalities are more common in this group, especially thymic follicular hyperplasia.[4] this subtype can be further divided into 2 groups:
- Early onset myasthenia gravis (onset of the disease before the age of 50 (EOMG)): In this group we have female predominance with the ratio of 3/1. Thymic follicular hyperplasia is more common in this group and is believed to be related to deregulation of sex hormones and their receptors on thymic cells.[5][6]
- These patients can have other autoimmune diseases like Hashimoto’s disease.[7]
- Late onset myasthenia gravis (onset of the disease after the age of 50 (LOMG)): Patients with this type of the disease can present with thymoma, a tumor of thymic epithelial cells.[8] In almost 50 percent of them we can find other antibodies like anti-ryanodine antibody, anti-titin antibody and anti-striated muscle antibody.[9] most of the patients in this group have severe symptoms like bulbar involvement.[10]
The forms without classical anti-AChR antibodies
This subtype can be further divided into 3 groups
- The form with anti-anti-MuSK antibodies: About 5 percent of MG patients, especially females has this antibody which belongs to IgG4 subclasses and cannot bind to complement.[11][12] their symptoms are mostly sever and involves facial, bulbar and respiratory muscles but spares ocular and thymic abnormalities.[11][13] In these patients both presynaptic and postsynaptic components of NMJ are affected and the severity of the disease is related to the amount of antibodies.[14][15]
- The form with anti-LRP4 antibodies: About 12-50 percent of patients who seems to be seronegative for anti-AchR and MuSK, presents antibody against LRP4.[16][17][18]
- The form with clustered AChR antibodies: 5 percent of patients with MG doesn’t have any antibodies but in 50 percent of them we can see clustered AchR with cell assay detection.[1]
Neonatal MG
- 10-20 percent of mothers with MG may have infants who display a transient neonatal myasthenia (TNM) for few days to 3 months.
- The cause of this condition is passive transfer of antibodies to the neonate.[19]
Congenital
- Congenital form of MG follows the Mendelian pattern and is caused by an error in the genes which are expressed in the NMJ.[20]
References
- ↑ 1.0 1.1 Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, Beeson D, Willcox N, Vincent A (July 2008). "IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis". Brain. 131 (Pt 7): 1940–52. doi:10.1093/brain/awn092. PMC 2442426. PMID 18515870.
- ↑ Vincent A, Newsom-Davis J (December 1985). "Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays". J. Neurol. Neurosurg. Psychiatry. 48 (12): 1246–52. PMC 1028609. PMID 4087000.
- ↑ Verschuuren JJ, Huijbers MG, Plomp JJ, Niks EH, Molenaar PC, Martinez-Martinez P, Gomez AM, De Baets MH, Losen M (July 2013). "Pathophysiology of myasthenia gravis with antibodies to the acetylcholine receptor, muscle-specific kinase and low-density lipoprotein receptor-related protein 4". Autoimmun Rev. 12 (9): 918–23. doi:10.1016/j.autrev.2013.03.001. PMID 23535160.
- ↑ Berrih S, Morel E, Gaud C, Raimond F, Le Brigand H, Bach JF (January 1984). "Anti-AChR antibodies, thymic histology, and T cell subsets in myasthenia gravis". Neurology. 34 (1): 66–71. PMID 6228745.
- ↑ Eymard B, Berrih-Aknin S (January 1995). "[Role of the thymus in the physiopathology of myasthenia]". Rev. Neurol. (Paris) (in French). 151 (1): 6–15. PMID 7676132.
- ↑ Nancy P, Berrih-Aknin S (May 2005). "Differential estrogen receptor expression in autoimmune myasthenia gravis". Endocrinology. 146 (5): 2345–53. doi:10.1210/en.2004-1003. PMC 1839841. PMID 15661863.
- ↑ Klein R, Marx A, Ströbel P, Schalke B, Nix W, Willcox N (September 2013). "Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis". Hum. Immunol. 74 (9): 1184–93. doi:10.1016/j.humimm.2013.06.020. PMID 23792059.
- ↑ Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P (July 2013). "The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes". Autoimmun Rev. 12 (9): 875–84. doi:10.1016/j.autrev.2013.03.007. PMID 23535159.
- ↑ Suzuki S, Utsugisawa K, Nagane Y, Suzuki N (2011). "Three types of striational antibodies in myasthenia gravis". Autoimmune Dis. 2011: 740583. doi:10.4061/2011/740583. PMC 3139883. PMID 21785709.
- ↑ Romi F, Aarli JA, Gilhus NE (June 2007). "Myasthenia gravis patients with ryanodine receptor antibodies have distinctive clinical features". Eur. J. Neurol. 14 (6): 617–20. doi:10.1111/j.1468-1331.2007.01785.x. PMID 17539937.
- ↑ 11.0 11.1 Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, Marino M, Bartoccioni E (October 2003). "Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis". Brain. 126 (Pt 10): 2304–11. doi:10.1093/brain/awg223. PMID 12821509.
- ↑ McConville J, Farrugia ME, Beeson D, Kishore U, Metcalfe R, Newsom-Davis J, Vincent A (April 2004). "Detection and characterization of MuSK antibodies in seronegative myasthenia gravis". Ann. Neurol. 55 (4): 580–4. doi:10.1002/ana.20061. PMID 15048899.
- ↑ Leite MI, Ströbel P, Jones M, Micklem K, Moritz R, Gold R, Niks EH, Berrih-Aknin S, Scaravilli F, Canelhas A, Marx A, Newsom-Davis J, Willcox N, Vincent A (March 2005). "Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG". Ann. Neurol. 57 (3): 444–8. doi:10.1002/ana.20386. PMID 15732104.
- ↑ Le Panse R, Berrih-Aknin S (October 2013). "Autoimmune myasthenia gravis: autoantibody mechanisms and new developments on immune regulation". Curr. Opin. Neurol. 26 (5): 569–76. doi:10.1097/WCO.0b013e328364d6cd. PMID 23995274.
- ↑ Bartoccioni E, Scuderi F, Minicuci GM, Marino M, Ciaraffa F, Evoli A (August 2006). "Anti-MuSK antibodies: correlation with myasthenia gravis severity". Neurology. 67 (3): 505–7. doi:10.1212/01.wnl.0000228225.23349.5d. PMID 16894117.
- ↑ Higuchi O, Hamuro J, Motomura M, Yamanashi Y (February 2011). "Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis". Ann. Neurol. 69 (2): 418–22. doi:10.1002/ana.22312. PMID 21387385.
- ↑ Pevzner A, Schoser B, Peters K, Cosma NC, Karakatsani A, Schalke B, Melms A, Kröger S (March 2012). "Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis". J. Neurol. 259 (3): 427–35. doi:10.1007/s00415-011-6194-7. PMID 21814823.
- ↑ Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, Xiong WC, Lisak RP, Tzartos SJ, Mei L (April 2012). "Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis". Arch. Neurol. 69 (4): 445–51. doi:10.1001/archneurol.2011.2393. PMID 22158716.
- ↑ Béhin A, Mayer M, Kassis-Makhoul B, Jugie M, Espil-Taris C, Ferrer X, Chatenoud L, Laforêt P, Eymard B (June 2008). "Severe neonatal myasthenia due to maternal anti-MuSK antibodies". Neuromuscul. Disord. 18 (6): 443–6. doi:10.1016/j.nmd.2008.03.006. PMID 18434154.
- ↑ Engel AG, Sine SM (June 2005). "Current understanding of congenital myasthenic syndromes". Curr Opin Pharmacol. 5 (3): 308–21. doi:10.1016/j.coph.2004.12.007. PMID 15907919.