Myasthenia gravis causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Causes
Myasthenia gravis may be caused by:
- Thymus abnormalities:
Thymus abnormalities including thymic hyperplasia and thymoma are very common in myasthenia gravis and thymectomy is one of the treatment of this disease.[1][2] In thymus, we have myoid cells which present intact AChR on their surface. On the other hand thymic epithelial cells produce AChR subunits which activate helper T cells. These T cells attack AChR on the myoid cells and the cascade of antibody production and complement activation will begin.[3][4][5]
- Genetic:
- The Major Histocompatibility Complex: In genetic etiology of most of the autoimmune diseases including MG, MHC genes play the most important role.[6]
- The CHRNA1 Locus: The translation product of this gene is the alpha subunit of AChR, which is the target of many autoantibodies in myasthenia gravis patients.[7]
- The PTPN22 Gene: This gene is responsible for producing an intracellular protein phosphatase PTPN22. The impaired binding of this protein to protein tyrosine kinase Csk occurs as a result of a missense polymorphism which replace arginine with tryptophan. Activity of PTPN22 will increase and inhibits T cell activation and interleukin 2 production which leads to predisposition to autoimmunity.[8][9]
- The FCGR2 Locus: Some studies investigated the relationship between polymorphism of FC receptors gene and MG and suggested that R arginine variant in type 2 (FCGR2) can be related to this disease.[10][11]
- The CTLA4 Locus: This gene is known to be responsible for many autoimmune diseases.[12]
- environment:
- Drugs: Drugs such as D-penicillamine[13], fludarabine[14], lithium carbonate[15] and botulinum toxin[16] can induce MG, and drugs such as curare, aminoglycosides, macrolides, fluoroquinolones, quinine, quinidine, procainamide, magnesium salts, calcium channel blockers, beta blockers, iodinated contrast agents and statins can worsen MG.[17][13]
- Infections:
- Trauma:
References
- ↑ Drachman DB (June 1994). "Myasthenia gravis". N. Engl. J. Med. 330 (25): 1797–810. doi:10.1056/NEJM199406233302507. PMID 8190158.
- ↑ Vincent A (October 2002). "Unravelling the pathogenesis of myasthenia gravis". Nat. Rev. Immunol. 2 (10): 797–804. doi:10.1038/nri916. PMID 12360217.
- ↑ Willcox N, Leite MI, Kadota Y, Jones M, Meager A, Subrahmanyam P, Dasgupta B, Morgan BP, Vincent A (2008). "Autoimmunizing mechanisms in thymoma and thymus". Ann. N. Y. Acad. Sci. 1132: 163–73. doi:10.1196/annals.1405.021. PMID 18567866.
- ↑ Leite MI, Jones M, Ströbel P, Marx A, Gold R, Niks E, Verschuuren JJ, Berrih-Aknin S, Scaravilli F, Canelhas A, Morgan BP, Vincent A, Willcox N (September 2007). "Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status". Am. J. Pathol. 171 (3): 893–905. doi:10.2353/ajpath.2007.070240. PMC 1959483. PMID 17675582.
- ↑ Hohlfeld R, Wekerle H (September 2008). "Reflections on the "intrathymic pathogenesis" of myasthenia gravis". J. Neuroimmunol. 201-202: 21–7. doi:10.1016/j.jneuroim.2008.05.020. PMID 18644632.
- ↑ Feltkamp TE, van den Berg-Loonen PM, Nijenhuis LE, Engelfriet CP, van Rossum AL, van Loghem JJ, Oosterhuis HJ (January 1974). "Myasthenia gravis, autoantibodies, and HL-A antigens". Br Med J. 1 (5899): 131–3. PMC 1633001. PMID 4544224.
- ↑ Tzartos SJ, Barkas T, Cung MT, Mamalaki A, Marraud M, Orlewski P, Papanastasiou D, Sakarellos C, Sakarellos-Daitsiotis M, Tsantili P, Tsikaris V (June 1998). "Anatomy of the antigenic structure of a large membrane autoantigen, the muscle-type nicotinic acetylcholine receptor". Immunol. Rev. 163: 89–120. PMID 9700504.
- ↑ Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, MacMurray J, Meloni GF, Lucarelli P, Pellecchia M, Eisenbarth GS, Comings D, Mustelin T (April 2004). "A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes". Nat. Genet. 36 (4): 337–8. doi:10.1038/ng1323. PMID 15004560.
- ↑ Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner VE, Gonzalez-Munoz A, Clark J, Veijola R, Cubbon R, Chen SL, Rosa R, Cumiskey AM, Serreze DV, Gregory S, Rogers J, Lyons PA, Healy B, Smink LJ, Todd JA, Peterson LB, Wicker LS, Santamaria P (March 2007). "Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity". Nat. Genet. 39 (3): 329–37. doi:10.1038/ng1958. PMC 2886969. PMID 17277778.
- ↑ Raknes G, Skeie GO, Gilhus NE, Aadland S, Vedeler C (January 1998). "FcgammaRIIA and FcgammaRIIIB polymorphisms in myasthenia gravis". J. Neuroimmunol. 81 (1–2): 173–6. PMID 9521619.
- ↑ van der Pol WL, Jansen MD, Kuks JB, de Baets M, Leppers-van de Straat FG, Wokke JH, van de Winkel JG, van den Berg LH (November 2003). "Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients". J. Neuroimmunol. 144 (1–2): 143–7. PMID 14597109.
- ↑ Kristiansen OP, Larsen ZM, Pociot F (February 2000). "CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity?". Genes Immun. 1 (3): 170–84. doi:10.1038/sj.gene.6363655. PMID 11196709.
- ↑ 13.0 13.1 Wittbrodt ET (February 1997). "Drugs and myasthenia gravis. An update". Arch. Intern. Med. 157 (4): 399–408. PMID 9046891.
- ↑ Fujimaki K, Takasaki H, Koharazawa H, Takabayashi M, Yamaji S, Baba Y, Kanamori H, Ishigatsubo Y (July 2005). "Idiopathic thrombocytopenic purpura and myasthenia gravis after fludarabine treatment for chronic lymphocytic leukemia". Leuk. Lymphoma. 46 (7): 1101–2. doi:10.1080/10428190500063054. PMID 16019566.
- ↑ Ronzière T, Auzou P, Ozsancak C, Magnier P, Sénant J, Hannequin D (2000). "[Myasthenic syndrome induced by lithium]". Presse Med (in French). 29 (19): 1043–4. PMID 10874911.
- ↑ Iwase T, Iwase C (March 2006). "Systemic effect of local and small-dose botulinum toxin injection to unmask subclinical myasthenia gravis". Graefes Arch. Clin. Exp. Ophthalmol. 244 (3): 415–6. doi:10.1007/s00417-005-0130-4. PMID 16175373.
- ↑ de Sousa E, Howard J (September 2008). "More evidence for the association between statins and myasthenia gravis". Muscle Nerve. 38 (3): 1085–6. doi:10.1002/mus.21072. PMID 18720505.