Anti-glutamate receptor antibodies

Anti-glutamate receptor antibodies are autoantibodies detected in serum and/or cerebrospinal fluid samples of a variety of disorders such as encephalitis, epilepsy and ataxia. Recent clinical and experimental studies suggest that these antibodies are not simply epiphenomena and are involved in autoimmune disease pathogenesis. The first anti-glutamate receptor antibody was shown by McNamara JO and colleagues to be directed against the GluR3 subunit of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Rogers SW, Andrews PI, Gahring LC, Whisenand T, Cauley K, Crain B, Hughes TE, Heinemann SF, McNamara JO. Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science. 1994 Jul 29;265(5172):648-51. ] Since then anti-GluR3 antibodies have been demonstrated in temporal lobe epilepsy, epilepsia partialis continua and focal epilepsy. Mantegazza R, Bernasconi P, Baggi F, Spreafico R, Ragona F, Antozzi C, Bernardi G, Granata T. Antibodies against GluR3 peptides are not specific for Rasmussen's encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol. 2002 Oct;131(1-2):179-85. ]

The second large group of anti-glutamate receptor antibodies is associated with different subunits of N-methyl-D-aspartate (NMDA) receptor. Patients with limbic encephalitis, encephalitis, systemic lupus erythematosus, ataxia and epilepsia partialis continua may present with serum and cerebrospinal fluid antibodies to the delta2 or NR2 subunits of the NMDA receptor. Shiihara T, Kato M, Konno A, Takahashi Y, Hayasaka K. Acute cerebellar ataxia and consecutive cerebellitis produced by glutamatereceptor delta2 autoantibody. Brain Dev. 2007 May;29(4):254-6. ] Hanly JG, Robichaud J, Fisk JD. Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. J Rheumatol. 2006 Aug;33(8):1553-8. ] Mochizuki Y, Mizutani T, Isozaki E, Ohtake T, Takahashi Y. Acute limbic encephalitis: a new entity? Neurosci Lett. 2006 Feb 6;394(1):5-8. ]

Antibodies against the NR1, NR2A and NR2B subunits of the NMDA receptor were described by Josep Dalmau, Erdem Tüzün and colleagues in women presenting with psychiatric symptoms, amnesia, seizures, dyskinesias, autonomic dysfunction and loss of consciousness. So far, these antibodies appear to be associated with an accompanying ovarian or mediastinal teratoma expressing NMDA receptors. Dalmau J, Tuzun E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007 Jan;61(1):25-36. ] Notably, this is the second neuronal cell surface antigen (after anti-voltage-gated potassium channel (VGKC) antibodies described by Angela Vincent and colleagues) associated with autoimmune encephalitis. Buckley C, Oger J, Clover L, Tuzun E, Carpenter K, Jackson M, Vincent A. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol. 2001 Jul;50(1):73-8. ]

Additionally, antibodies to the mGluR1 subunit of the metabotropic glutamate receptor have been shown in a small group of ataxia patients. Coesmans M, Smitt PA, Linden DJ, Shigemoto R, Hirano T, Yamakawa Y, van Alphen AM, Luo C, van der Geest JN, Kros JM, Gaillard CA, Frens MA, de Zeeuw CI. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Ann Neurol. 2003 Mar;53(3):325-36. ] Anti-glutamate receptor antibodies are also detected in various non-immunological neurological diseases such as stroke and trauma. During MJ, Symes CW, Lawlor PA, Lin J, Dunning J, Fitzsimons HL, Poulsen D, Leone P, Xu R, Dicker BL, Lipski J, Young D. An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science. 2000 Feb 25;287(5457):1453-60. ] Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiacsurgery in high-risk patients. Stroke. 2006 Jun;37(6):1432-6. ]

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