Introduction: Myasthenia gravis (MG) is an autoimmune disease with weakness in striated musculature due to anti-acetylcholine receptor (AChR) antibodies or muscle specific kinase at the neuromuscular junction. A subgroup of patients has periocular symptoms only; ocular MG (OMG). Matrix metalloproteinases (MMP) are increased in several autoimmune diseases, including generalized MG (GMG), and have been suggested to play a role in immune cell infiltration, basement membrane breakdown and autoimmune pathogenesis. Methods: Total levels of MMP2, MMP3 and MMP9 were measured in serum by ELISA. Results: The MG patients had increased serum levels of MMP2 (median values 200.7 vs. 159.7 ng/ml, p < 0.001) and MMP9 (median values 629.6 vs. 386.4 ng/ml, p < 0.001) compared to controls. A subgroup of patients had increased MMP3 concentration (p = 0.001). The differences were not dependent on presence of AChR antibodies. No difference was observed between GMG and OMG patients with regard to MMP2 (p = 0.598), MMP3 (p = 0.450) and MMP9 (p = 0.271). Discussion: The increased MMP levels in our MG patients group and the lack of dependence on anti-AChR antibodies suggest that MMP2, MMP3 and MMP9 play a role in the development of MG. The similarities between GMG and OMG support OMG as a systemic disease.

Conti-Fine BM, Milani M, Kaminski HJ: Myasthenia gravis: past, present, and future. J Clin Invest 2006;116:2843–2854.
Romi F, et al: Striational antibodies in myasthenia gravis: reactivity and possible clinical significance. Arch Neurol 2005;62:442–446.
Gilbert ME, Savino PJ: Ocular myasthenia gravis. Int Ophthalmol Clin 2007;47:93–103, ix.
Evoli A, et al: Therapeutic options in ocular myasthenia gravis. Neuromuscul Disord 2001;11:208–216.
Luchanok U, Kaminski HJ: Ocular myasthenia: diagnostic and treatment recommendations and the evidence base. Curr Opin Neurol 2008;21:8–15.
Juel VC, Massey JM: Myasthenia gravis. Orphanet J Rare Dis 2007;2:44.
Morrison CJ, et al: Matrix metalloproteinase proteomics: substrates, targets, and therapy. Curr Opin Cell Biol 2009;21:645–653.
Murphy, G. and H. Nagase, Progress in matrix metalloproteinase research. Mol Aspects Med 2008;29:290–308.
Romi FR, Gilhus NE, Luckman SP: Serum matrix metalloproteinase-3 levels are elevated in myasthenia gravis. J Neuroimmunol 2008;195:96–99.
Kobayashi A, et al: Serum levels of matrix metalloproteinase 3 (stromelysin 1) for monitoring synovitis in rheumatoid arthritis. Arch Pathol Lab Med 2007;131:563–570.
Kotajima L, et al: Increased levels of matrix metalloproteinase-3 in sera from patients with active lupus nephritis. Clin Exp Rheumatol 1998;16:409–415.
Chen WS, et al: Autoantibody and biopsy grading are associated with expression of ICAM-1, MMP-3, and TRAIL in salivary gland mononuclear cells of Chinese patients with Sjogren’s syndrome. J Rheumatol 2009;36:989–996.
Witzemann V: Development of the neuromuscular junction. Cell Tissue Res 2006;326:263–271.
Matache C, et al: Matrix metalloproteinase-9 and its natural inhibitor TIMP-1 expressed or secreted by peripheral blood mononuclear cells from patients with systemic lupus erythematosus. J Autoimmun 2003;20:323–331.
Kim WU, et al: Elevated matrix metalloproteinase-9 in patients with systemic sclerosis. Arthritis Res Ther 2005;7:R71–79.
Gruber BL, et al: Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially useful laboratory marker. Clin Immunol Immunopathol 1996;78:161–171.
Konttinen YT, et al: Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjögren’s syndrome. Matrix Biol 1998;17:335–347.
Yong VW, et al: Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators. J Neurol Sci 2007;259:79–84.
Chakraborti S, et al: Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 2003;253:269–285.
Ogata Y, Enghild JJ, Nagase H: Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 1992;267:3581–3584.
Vempati P, Karagiannis ED, Popel AS: A biochemical model of matrix metalloproteinase 9 activation and inhibition. J Biol Chem 2007;282:37585–37596.
VanSaun M, et al: Activation of matrix metalloproteinase-3 is altered at the frog neuromuscular junction following changes in synaptic activity. Dev Neurobiol 2007;67:1488–1497.
Chang YH, et al: Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin Biochem 2008;41:955–959.
Shiau MY, et al: Increased circulatory MMP-2 and MMP-9 levels and activities in patients with type 1 diabetes mellitus. Mt Sinai J Med 2006;73:1024–1028.
Zhao XL, et al: MMP-mediated cleavage of beta-dystroglycan in myelin sheath is involved in autoimmune neuritis. Biochem Biophys Res Commun 2010;392:551–556.
Brundula V, et al: Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis. Brain 2002;125:1297–1308.
Hurnaus S, et al: Serum levels of matrix metalloproteinases-2 and -9 and their tissue inhibitors in inflammatory neuromuscular disorders. Eur Neurol 2006;55:204–208.
Kherif S, et al: Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: a study in experimentally injured and MDX muscles. Dev Biol 1999;205:158–170.
Demestre M, et al: Characterization of matrix metalloproteinases in denervated muscle. Neuropathol Appl Neurobiol 2005;31:545–555.
Zamecnik J, et al: Muscle lymphocytic infiltrates in thymoma-associated myasthenia gravis are phenotypically different from those in polymyositis. Neuromuscul Disord 2007;17:935–942.
Kumagai K, et al: Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma. J Immunol 1999;162:4212–4219.
Cai Y, Chen T, Xu Q: Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration. J Pharm Pharmacol 2003;55:691–696.
Marracci GH, et al: Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J Neuroimmunol 2002;131:104–114.
Werle MJ, VanSaun M: Activity dependent removal of agrin from synaptic basal lamina by matrix metalloproteinase 3. J Neurocytol 2003;32:905–913.
Vincent A: Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol 2002;2:797–804.
Drachman DB: Myasthenia gravis. N Engl J Med 1994;330:1797–1810.
Leite MI, et al: IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain 2008;131:1940–1952.
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