Myasthenia gravis pathophysiology: Difference between revisions

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{{Myasthenia gravis}}
{{Myasthenia gravis}}


{{CMG}}
{{CMG}} {{Fs}}
==Overview==
==Overview==
Myasthenia gravis is a [[neuromuscular disease]] caused by an [[autoimmune]] reactions. The main problem in this disease is the abnormal transmission of [[nerve impulses]] to [[muscle fibers]] in [[Neuromuscular junction|NMJ]]. Genes involved in the pathogenesis of Myasthenia gravis include: [[MHC|The Major Histocompatibility Complex]], the [[CHRNA1]] [[Locus]], the [[PTPN22]] [[Gene]], the [[FCGR2A|FCGR2]] [[Locus]] and the [[CTLA-4|CTLA4]] [[Locus]].


==Pathophysiology==
==Pathophysiology==
Line 33: Line 34:


== Genetics ==
== Genetics ==
[Disease name] is transmitted in [mode of genetic transmission] pattern.
Genes involved in the pathogenesis of Myasthenia gravis include:
* [[MHC|The Major Histocompatibility Complex]]: In genetic etiology of most of the [[autoimmune diseases]] including [[Myasthenia gravis|MG]], [[MHC]] genes play the most important role.<ref name="pmid4544224">{{cite journal |vauthors=Feltkamp TE, van den Berg-Loonen PM, Nijenhuis LE, Engelfriet CP, van Rossum AL, van Loghem JJ, Oosterhuis HJ |title=Myasthenia gravis, autoantibodies, and HL-A antigens |journal=Br Med J |volume=1 |issue=5899 |pages=131–3 |date=January 1974 |pmid=4544224 |pmc=1633001 |doi= |url=}}</ref>
* The [[CHRNA1]] [[Locus]]: The [[Translation (genetics)|translation]] product of this [[gene]] is the alpha subunit of [[Acetylcholine receptor|AChR]], which is the target of many [[autoantibodies]] in myasthenia gravis patients.<ref name="pmid9700504">{{cite journal |vauthors=Tzartos SJ, Barkas T, Cung MT, Mamalaki A, Marraud M, Orlewski P, Papanastasiou D, Sakarellos C, Sakarellos-Daitsiotis M, Tsantili P, Tsikaris V |title=Anatomy of the antigenic structure of a large membrane autoantigen, the muscle-type nicotinic acetylcholine receptor |journal=Immunol. Rev. |volume=163 |issue= |pages=89–120 |date=June 1998 |pmid=9700504 |doi= |url=}}</ref>
* 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]].<ref name="pmid15004560">{{cite journal |vauthors=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 |title=A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes |journal=Nat. Genet. |volume=36 |issue=4 |pages=337–8 |date=April 2004 |pmid=15004560 |doi=10.1038/ng1323 |url=}}</ref><ref name="pmid17277778">{{cite journal |vauthors=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 |title=Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity |journal=Nat. Genet. |volume=39 |issue=3 |pages=329–37 |date=March 2007 |pmid=17277778 |pmc=2886969 |doi=10.1038/ng1958 |url=}}</ref>
* The [[FCGR2A|FCGR2]] [[Locus]]: Some studies investigated the relationship between [[Polymorphisms|polymorphism]] of FC receptors [[gene]] and [[Myasthenia gravis|MG]] and suggested that R arginine variant in type 2 (FCGR2) can be related to this disease.<ref name="pmid9521619">{{cite journal |vauthors=Raknes G, Skeie GO, Gilhus NE, Aadland S, Vedeler C |title=FcgammaRIIA and FcgammaRIIIB polymorphisms in myasthenia gravis |journal=J. Neuroimmunol. |volume=81 |issue=1-2 |pages=173–6 |date=January 1998 |pmid=9521619 |doi= |url=}}</ref><ref name="pmid14597109">{{cite journal |vauthors=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 |title=Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients |journal=J. Neuroimmunol. |volume=144 |issue=1-2 |pages=143–7 |date=November 2003 |pmid=14597109 |doi= |url=}}</ref>
* The [[CTLA-4|CTLA4]] [[Locus]]: This [[gene]] is known to be responsible for many [[autoimmune diseases]].<ref name="pmid11196709">{{cite journal |vauthors=Kristiansen OP, Larsen ZM, Pociot F |title=CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity? |journal=Genes Immun. |volume=1 |issue=3 |pages=170–84 |date=February 2000 |pmid=11196709 |doi=10.1038/sj.gene.6363655 |url=}}</ref>


OR
== Associated Conditions ==
Conditions associated with Myasthenia gravis include:
* 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.<ref name="pmid8190158">{{cite journal |vauthors=Drachman DB |title=Myasthenia gravis |journal=N. Engl. J. Med. |volume=330 |issue=25 |pages=1797–810 |date=June 1994 |pmid=8190158 |doi=10.1056/NEJM199406233302507 |url=}}</ref><ref name="pmid12360217">{{cite journal |vauthors=Vincent A |title=Unravelling the pathogenesis of myasthenia gravis |journal=Nat. Rev. Immunol. |volume=2 |issue=10 |pages=797–804 |date=October 2002 |pmid=12360217 |doi=10.1038/nri916 |url=}}</ref>


Genes involved in the pathogenesis of [disease name] include:
==Gross Pathology==
* [Gene1]
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* [Gene2]
* [Gene3]
OR


The development of [disease name] is the result of multiple genetic mutations such as:
* [Mutation 1]
* [Mutation 2]
* [Mutation 3]
== Associated Conditions ==
Conditions associated with [disease name] include:
* [Condition 1]
* [Condition 2]
* [Condition 3]


== Microscopic Pathology ==
== Microscopic Pathology ==

Latest revision as of 00:46, 13 September 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Fahimeh Shojaei, M.D.

Overview

Myasthenia gravis is a neuromuscular disease caused by an autoimmune reactions. The main problem in this disease is the abnormal transmission of nerve impulses to muscle fibers in NMJ. Genes involved in the pathogenesis of Myasthenia gravis include: The Major Histocompatibility Complex, the CHRNA1 Locus, the PTPN22 Gene, the FCGR2 Locus and the CTLA4 Locus.

Pathophysiology

Physiology

Pathogenesis

Genetics

Genes involved in the pathogenesis of Myasthenia gravis include:

Associated Conditions

Conditions associated with Myasthenia gravis include:

  • 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.[31][32]

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


References

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  18. Nauert JB, Klauck TM, Langeberg LK, Scott JD (January 1997). "Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein". Curr. Biol. 7 (1): 52–62. PMID 9000000.
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  21. Christadoss P, Goluszko E (January 2002). "Treatment of experimental autoimmune myasthenia gravis with recombinant human tumor necrosis factor receptor Fc protein". J. Neuroimmunol. 122 (1–2): 186–90. PMID 11777558.
  22. Feferman T, Maiti PK, Berrih-Aknin S, Bismuth J, Bidault J, Fuchs S, Souroujon MC (May 2005). "Overexpression of IFN-induced protein 10 and its receptor CXCR3 in myasthenia gravis". J. Immunol. 174 (9): 5324–31. PMID 15843529.
  23. Shi FD, Wang HB, Li H, Hong S, Taniguchi M, Link H, Van Kaer L, Ljunggren HG (September 2000). "Natural killer cells determine the outcome of B cell-mediated autoimmunity". Nat. Immunol. 1 (3): 245–51. doi:10.1038/79792. PMID 10973283.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. Drachman DB (June 1994). "Myasthenia gravis". N. Engl. J. Med. 330 (25): 1797–810. doi:10.1056/NEJM199406233302507. PMID 8190158.
  32. Vincent A (October 2002). "Unravelling the pathogenesis of myasthenia gravis". Nat. Rev. Immunol. 2 (10): 797–804. doi:10.1038/nri916. PMID 12360217.

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