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Published in: Journal of Neurology 4/2012

01-04-2012 | Review

Systemic lupus erythematosus, the brain, and anti-NR2 antibodies

Authors: Maria B. Lauvsnes, Roald Omdal

Published in: Journal of Neurology | Issue 4/2012

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Abstract

Neurological and psychiatric disorders are common in patients with systemic lupus erythematosus (SLE). While several pathogenetic mechanisms are thought to be involved, among of the most challenging and best investigated are antibodies against the N-methyl-d-aspartate (NMDA) receptor subtypes 2a and 2b (anti-NR2 antibodies). This review summarizes the most relevant mechanisms for neuropsychiatric (NP) involvement in SLE (NPSLE) with special emphasis on the role of anti-NR2 antibodies and provides an overview of published articles on anti-NR2 antibodies and brain involvement as of May 2011. In mice, neuronal cell death occurs when anti-NR2 antibodies gain access to the brain, either by injection directly into the brain, or by systemic immunization and abrogation of the blood–brain barrier. Either impaired memory and hippocampal atrophy, or emotional disturbances and atrophy of the amygdala follow, seemingly dependent on the method used for disruption of the blood–brain barrier. Recent studies indicate that the effect of anti-NR2 antibodies is dose dependent; at low concentrations they alter synaptic function; at higher concentrations they can cause neuronal cell death by apoptosis. An association between anti-NR2 antibodies and NPSLE has been confirmed in 6 out of 13 human studies; the manifestations are primarily of diffuse cerebral character.
Literature
1.
go back to reference Abbott NJ, Mendonca LL, Dolman DE (2003) The blood-brain barrier in systemic lupus erythematosus. Lupus 12:908–915PubMedCrossRef Abbott NJ, Mendonca LL, Dolman DE (2003) The blood-brain barrier in systemic lupus erythematosus. Lupus 12:908–915PubMedCrossRef
2.
go back to reference Abreu MR, Jakosky A, Folgerini M, Brenol JC, Xavier RM, Kapczinsky F (2005) Neuropsychiatric systemic lupus erythematosus: correlation of brain MR imaging, CT, and SPECT. Clin Imaging 29:215–221PubMedCrossRef Abreu MR, Jakosky A, Folgerini M, Brenol JC, Xavier RM, Kapczinsky F (2005) Neuropsychiatric systemic lupus erythematosus: correlation of brain MR imaging, CT, and SPECT. Clin Imaging 29:215–221PubMedCrossRef
3.
go back to reference ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608 ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608
4.
go back to reference Ainiala H, Dastidar P, Loukkola J, Lehtimaki T, Korpela M, Peltola J, Hietaharju A (2005) Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol 34:376–382PubMedCrossRef Ainiala H, Dastidar P, Loukkola J, Lehtimaki T, Korpela M, Peltola J, Hietaharju A (2005) Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population-based study. Scand J Rheumatol 34:376–382PubMedCrossRef
5.
go back to reference Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A (2001) The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 57:496–500PubMed Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A (2001) The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neurology 57:496–500PubMed
6.
go back to reference Alcocer-Varela J, Aleman-Hoey D, Alarcon-Segovia D (1992) Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers. Lupus 1:111–117PubMedCrossRef Alcocer-Varela J, Aleman-Hoey D, Alarcon-Segovia D (1992) Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers. Lupus 1:111–117PubMedCrossRef
7.
go back to reference Appenzeller S, Cendes F, Costallat LT (2009) Cognitive impairment and employment status in systemic lupus erythematosus: a prospective longitudinal study. Arthritis Rheum 61:680–687PubMedCrossRef Appenzeller S, Cendes F, Costallat LT (2009) Cognitive impairment and employment status in systemic lupus erythematosus: a prospective longitudinal study. Arthritis Rheum 61:680–687PubMedCrossRef
8.
go back to reference Arinuma Y, Yanagida T, Hirohata S (2008) Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 58:1130–1135PubMedCrossRef Arinuma Y, Yanagida T, Hirohata S (2008) Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 58:1130–1135PubMedCrossRef
9.
go back to reference Brey RL, Holliday SL, Saklad AR, Navarrete MG, Hermosillo-Romo D, Stallworth CL, Valdez CR, Escalante A, del Rincon I, Gronseth G, Rhine CB, Padilla P, McGlasson D (2002) Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 58:1214–1220PubMed Brey RL, Holliday SL, Saklad AR, Navarrete MG, Hermosillo-Romo D, Stallworth CL, Valdez CR, Escalante A, del Rincon I, Gronseth G, Rhine CB, Padilla P, McGlasson D (2002) Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Neurology 58:1214–1220PubMed
10.
go back to reference Carbotte RM, Denburg SD, Denburg JA (1986) Prevalence of cognitive impairment in systemic lupus erythematosus. J Nerv Ment Dis 174:357–364PubMedCrossRef Carbotte RM, Denburg SD, Denburg JA (1986) Prevalence of cognitive impairment in systemic lupus erythematosus. J Nerv Ment Dis 174:357–364PubMedCrossRef
11.
go back to reference Carlomagno S, Migliaresi S, Ambrosone L, Sannino M, Sanges G, Di Iorio G (2000) Cognitive impairment in systemic lupus erythematosus: a follow-up study. J Neurol 247:273–279PubMedCrossRef Carlomagno S, Migliaresi S, Ambrosone L, Sannino M, Sanges G, Di Iorio G (2000) Cognitive impairment in systemic lupus erythematosus: a follow-up study. J Neurol 247:273–279PubMedCrossRef
12.
13.
go back to reference Deapen D, Escalante A, Weinrib L, Horwitz D, Bachman B, Roy-Burman P, Walker A, Mack TM (1992) A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 35:311–318PubMedCrossRef Deapen D, Escalante A, Weinrib L, Horwitz D, Bachman B, Roy-Burman P, Walker A, Mack TM (1992) A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 35:311–318PubMedCrossRef
14.
go back to reference DeGiorgio LA, Konstantinov KN, Lee SC, Hardin JA, Volpe BT, Diamond B (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7:1189–1193PubMedCrossRef DeGiorgio LA, Konstantinov KN, Lee SC, Hardin JA, Volpe BT, Diamond B (2001) A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med 7:1189–1193PubMedCrossRef
15.
go back to reference Dellalibera-Joviliano R, Dos Reis ML, Cunha Fde Q, Donadi EA (2003) Kinins and cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus. J Rheumatol 30:485–492PubMed Dellalibera-Joviliano R, Dos Reis ML, Cunha Fde Q, Donadi EA (2003) Kinins and cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus. J Rheumatol 30:485–492PubMed
16.
go back to reference Devinsky O, Petito CK, Alonso DR (1988) Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol 23:380–384PubMedCrossRef Devinsky O, Petito CK, Alonso DR (1988) Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol 23:380–384PubMedCrossRef
17.
go back to reference Edworthy S (2004) Clinical manifestations of systemic lupus erythematosus. In: Harris ED, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, Sledge CB (eds) Kelley’s textbook of rheumatology, 7th edn. Elsevier Saunders, pp 1204–1215 Edworthy S (2004) Clinical manifestations of systemic lupus erythematosus. In: Harris ED, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, Sledge CB (eds) Kelley’s textbook of rheumatology, 7th edn. Elsevier Saunders, pp 1204–1215
18.
go back to reference Eilertsen GO, Becker-Merok A, Nossent JC (2009) The influence of the 1997 updated classification criteria for systemic lupus erythematosus: epidemiology, disease presentation, and patient management. J Rheumatol 36:552–559PubMedCrossRef Eilertsen GO, Becker-Merok A, Nossent JC (2009) The influence of the 1997 updated classification criteria for systemic lupus erythematosus: epidemiology, disease presentation, and patient management. J Rheumatol 36:552–559PubMedCrossRef
19.
go back to reference Ellis SG, Verity MA (1979) Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977. Semin Arthritis Rheum 8:212–221PubMedCrossRef Ellis SG, Verity MA (1979) Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977. Semin Arthritis Rheum 8:212–221PubMedCrossRef
20.
go back to reference Ellison G (1995) The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Res Brain Res Rev 20:250–267PubMedCrossRef Ellison G (1995) The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Res Brain Res Rev 20:250–267PubMedCrossRef
21.
go back to reference Faust TW, Chang EH, Kowal C, Berlin R, Gazaryan IG, Bertini E, Zhang J, Sanchez-Guerrero J, Fragoso-Loyo HE, Volpe BT, Diamond B, Huerta PT (2010) Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci USA 107:18569–18574PubMedCrossRef Faust TW, Chang EH, Kowal C, Berlin R, Gazaryan IG, Bertini E, Zhang J, Sanchez-Guerrero J, Fragoso-Loyo HE, Volpe BT, Diamond B, Huerta PT (2010) Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms. Proc Natl Acad Sci USA 107:18569–18574PubMedCrossRef
22.
go back to reference Fragoso-Loyo H, Cabiedes J, Orozco-Narvaez A, Davila-Maldonado L, Atisha-Fregoso Y, Diamond B, Llorente L, Sanchez-Guerrero J (2008) Serum and cerebrospinal fluid autoantibodies in patients with neuropsychiatric lupus erythematosus. Implications for diagnosis and pathogenesis. PLoS ONE 3(10):e3347PubMedCrossRef Fragoso-Loyo H, Cabiedes J, Orozco-Narvaez A, Davila-Maldonado L, Atisha-Fregoso Y, Diamond B, Llorente L, Sanchez-Guerrero J (2008) Serum and cerebrospinal fluid autoantibodies in patients with neuropsychiatric lupus erythematosus. Implications for diagnosis and pathogenesis. PLoS ONE 3(10):e3347PubMedCrossRef
23.
go back to reference Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jonsen A, Bengtsson AA, Rantapaa-Dahlqvist S, Baechler EC, Brown EE, Alarcon GS, Edberg JC, Ramsey-Goldman R, McGwin G Jr, Reveille JD, Vila LM, Kimberly RP, Manzi S, Petri MA, Lee A, Gregersen PK, Seldin MF, Ronnblom L, Criswell LA, Syvanen AC, Behrens TW, Graham RR (2009) A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 41:1228–1233PubMedCrossRef Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jonsen A, Bengtsson AA, Rantapaa-Dahlqvist S, Baechler EC, Brown EE, Alarcon GS, Edberg JC, Ramsey-Goldman R, McGwin G Jr, Reveille JD, Vila LM, Kimberly RP, Manzi S, Petri MA, Lee A, Gregersen PK, Seldin MF, Ronnblom L, Criswell LA, Syvanen AC, Behrens TW, Graham RR (2009) A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 41:1228–1233PubMedCrossRef
24.
go back to reference Goff DC, Coyle JT (2001) The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 158:1367–1377PubMedCrossRef Goff DC, Coyle JT (2001) The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 158:1367–1377PubMedCrossRef
25.
go back to reference Gono T, Kawaguchi Y, Kaneko H, Nishimura K, Hanaoka M, Kataoka S, Okamoto Y, Katsumata Y, Yamanaka H (2011) Anti-NR2A antibody as a predictor for neuropsychiatric systemic lupus erythematosus. Rheumatology (Oxford) 50:1578–1585 Gono T, Kawaguchi Y, Kaneko H, Nishimura K, Hanaoka M, Kataoka S, Okamoto Y, Katsumata Y, Yamanaka H (2011) Anti-NR2A antibody as a predictor for neuropsychiatric systemic lupus erythematosus. Rheumatology (Oxford) 50:1578–1585
26.
go back to reference Graham RR, Ortmann WA, Langefeld CD, Jawaheer D, Selby SA, Rodine PR, Baechler EC, Rohlf KE, Shark KB, Espe KJ, Green LE, Nair RP, Stuart PE, Elder JT, King RA, Moser KL, Gaffney PM, Bugawan TL, Erlich HA, Rich SS, Gregersen PK, Behrens TW (2002) Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus. Am J Hum Genet 71:543–553PubMedCrossRef Graham RR, Ortmann WA, Langefeld CD, Jawaheer D, Selby SA, Rodine PR, Baechler EC, Rohlf KE, Shark KB, Espe KJ, Green LE, Nair RP, Stuart PE, Elder JT, King RA, Moser KL, Gaffney PM, Bugawan TL, Erlich HA, Rich SS, Gregersen PK, Behrens TW (2002) Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus. Am J Hum Genet 71:543–553PubMedCrossRef
27.
go back to reference Hanly JG, Hong C, Smith S, Fisk JD (1999) A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 42:728–734PubMedCrossRef Hanly JG, Hong C, Smith S, Fisk JD (1999) A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum 42:728–734PubMedCrossRef
28.
go back to reference Hanly JG, McCurdy G, Fougere L, Douglas JA, Thompson K (2004) Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J Rheumatol 31:2156–2162PubMed Hanly JG, McCurdy G, Fougere L, Douglas JA, Thompson K (2004) Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J Rheumatol 31:2156–2162PubMed
29.
go back to reference Hanly JG, Robichaud J, Fisk JD (2006) Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. J Rheumatol 33:1553–1558PubMed Hanly JG, Robichaud J, Fisk JD (2006) Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. J Rheumatol 33:1553–1558PubMed
30.
go back to reference Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg D, Alarcon GS, Clarke A, Bernatsky S, Merrill JT, Petri M, Dooley MA, Gladman D, Fortin PR, Steinsson K, Bruce I, Manzi S, Khamashta M, Zoma A, Aranow C, Ginzler E, Van Vollenhoven R, Font J, Sturfelt G, Nived O, Ramsey-Goldman R, Kalunian K, Douglas J, Thompson K, Farewell V, Systemic Lupus International Collaborating C (2007) Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum 56:265–273PubMedCrossRef Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg D, Alarcon GS, Clarke A, Bernatsky S, Merrill JT, Petri M, Dooley MA, Gladman D, Fortin PR, Steinsson K, Bruce I, Manzi S, Khamashta M, Zoma A, Aranow C, Ginzler E, Van Vollenhoven R, Font J, Sturfelt G, Nived O, Ramsey-Goldman R, Kalunian K, Douglas J, Thompson K, Farewell V, Systemic Lupus International Collaborating C (2007) Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum 56:265–273PubMedCrossRef
31.
go back to reference Hanly JG, Urowitz MB, Siannis F, Farewell V, Gordon C, Bae SC, Isenberg D, Dooley MA, Clarke A, Bernatsky S, Gladman D, Fortin PR, Manzi S, Steinsson K, Bruce IN, Ginzler E, Aranow C, Wallace DJ, Ramsey-Goldman R, van Vollenhoven R, Sturfelt G, Nived O, Sanchez-Guerrero J, Alarcon GS, Petri M, Khamashta M, Zoma A, Font J, Kalunian K, Douglas J, Qi Q, Thompson K, Merrill JT, Systemic Lupus International Collaborating C (2008) Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum 58:843–853PubMedCrossRef Hanly JG, Urowitz MB, Siannis F, Farewell V, Gordon C, Bae SC, Isenberg D, Dooley MA, Clarke A, Bernatsky S, Gladman D, Fortin PR, Manzi S, Steinsson K, Bruce IN, Ginzler E, Aranow C, Wallace DJ, Ramsey-Goldman R, van Vollenhoven R, Sturfelt G, Nived O, Sanchez-Guerrero J, Alarcon GS, Petri M, Khamashta M, Zoma A, Font J, Kalunian K, Douglas J, Qi Q, Thompson K, Merrill JT, Systemic Lupus International Collaborating C (2008) Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum 58:843–853PubMedCrossRef
32.
go back to reference Hanly JG, Walsh NM, Sangalang V (1992) Brain pathology in systemic lupus erythematosus. J Rheumatol 19:732–741PubMed Hanly JG, Walsh NM, Sangalang V (1992) Brain pathology in systemic lupus erythematosus. J Rheumatol 19:732–741PubMed
33.
go back to reference Harboe E, Tjensvoll AB, Maroni S, Goransson LG, Greve OJ, Beyer MK, Herigstad A, Kvaloy JT, Omdal R (2009) Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjogren syndrome: a comparative population-based study. Ann Rheum Dis 68:1541–1546PubMedCrossRef Harboe E, Tjensvoll AB, Maroni S, Goransson LG, Greve OJ, Beyer MK, Herigstad A, Kvaloy JT, Omdal R (2009) Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjogren syndrome: a comparative population-based study. Ann Rheum Dis 68:1541–1546PubMedCrossRef
34.
go back to reference Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GR (1983) Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 2:1211–1214PubMedCrossRef Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GR (1983) Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 2:1211–1214PubMedCrossRef
35.
go back to reference Harrison MJ, Ravdin LD, Lockshin MD (2006) Relationship between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus. Arthritis Rheum 54:2515–2522PubMedCrossRef Harrison MJ, Ravdin LD, Lockshin MD (2006) Relationship between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus. Arthritis Rheum 54:2515–2522PubMedCrossRef
36.
go back to reference Hirohata S, Arinuma Y, Takayama M, Yoshio T (2007) Association of cerebrospinal fluid anti-ribosomal P protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther 9:R44PubMedCrossRef Hirohata S, Arinuma Y, Takayama M, Yoshio T (2007) Association of cerebrospinal fluid anti-ribosomal P protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther 9:R44PubMedCrossRef
37.
go back to reference Hirohata S, Miyamoto T (1990) Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 33:644–649PubMedCrossRef Hirohata S, Miyamoto T (1990) Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 33:644–649PubMedCrossRef
38.
go back to reference Hossain M, Sathe T, Fazio V, Mazzone P, Weksler B, Janigro D, Rapp E, Cucullo L (2009) Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier. Brain Res 1287:192–205PubMedCrossRef Hossain M, Sathe T, Fazio V, Mazzone P, Weksler B, Janigro D, Rapp E, Cucullo L (2009) Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier. Brain Res 1287:192–205PubMedCrossRef
39.
go back to reference Huerta PT, Kowal C, DeGiorgio LA, Volpe BT, Diamond B (2006) Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci USA 103:678–683PubMedCrossRef Huerta PT, Kowal C, DeGiorgio LA, Volpe BT, Diamond B (2006) Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci USA 103:678–683PubMedCrossRef
40.
go back to reference Husebye ES, Sthoeger ZM, Dayan M, Zinger H, Elbirt D, Levite M, Mozes E (2005) Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Ann Rheum Dis 64:1210–1213PubMedCrossRef Husebye ES, Sthoeger ZM, Dayan M, Zinger H, Elbirt D, Levite M, Mozes E (2005) Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Ann Rheum Dis 64:1210–1213PubMedCrossRef
41.
go back to reference Isshi K, Hirohata S (1996) Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 39:1483–1490PubMedCrossRef Isshi K, Hirohata S (1996) Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 39:1483–1490PubMedCrossRef
42.
go back to reference Isshi K, Hirohata S (1998) Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus. Arthritis Rheum 41:1819–1827PubMedCrossRef Isshi K, Hirohata S (1998) Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus. Arthritis Rheum 41:1819–1827PubMedCrossRef
43.
go back to reference Johnson RT, Richardson EP (1968) The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore) 47:337–369CrossRef Johnson RT, Richardson EP (1968) The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore) 47:337–369CrossRef
44.
go back to reference Karassa FB, Afeltra A, Ambrozic A, Chang DM, De Keyser F, Doria A, Galeazzi M, Hirohata S, Hoffman IE, Inanc M, Massardo L, Mathieu A, Mok CC, Morozzi G, Sanna G, Spindler AJ, Tzioufas AG, Yoshio T, Ioannidis JP (2006) Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum 54:312–324PubMedCrossRef Karassa FB, Afeltra A, Ambrozic A, Chang DM, De Keyser F, Doria A, Galeazzi M, Hirohata S, Hoffman IE, Inanc M, Massardo L, Mathieu A, Mok CC, Morozzi G, Sanna G, Spindler AJ, Tzioufas AG, Yoshio T, Ioannidis JP (2006) Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum 54:312–324PubMedCrossRef
45.
go back to reference Kowal C, Degiorgio LA, Lee JY, Edgar MA, Huerta PT, Volpe BT, Diamond B (2006) Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A 103:19854–19859PubMedCrossRef Kowal C, Degiorgio LA, Lee JY, Edgar MA, Huerta PT, Volpe BT, Diamond B (2006) Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A 103:19854–19859PubMedCrossRef
46.
go back to reference Kowal C, DeGiorgio LA, Nakaoka T, Hetherington H, Huerta PT, Diamond B, Volpe BT (2004) Cognition and immunity; antibody impairs memory. Immunity 21:179–188PubMedCrossRef Kowal C, DeGiorgio LA, Nakaoka T, Hetherington H, Huerta PT, Diamond B, Volpe BT (2004) Cognition and immunity; antibody impairs memory. Immunity 21:179–188PubMedCrossRef
47.
go back to reference Kozora E, Arciniegas DB, Zhang L, West S (2007) Neuropsychological patterns in systemic lupus erythematosus patients with depression. Arthritis Res Ther 9:R48PubMedCrossRef Kozora E, Arciniegas DB, Zhang L, West S (2007) Neuropsychological patterns in systemic lupus erythematosus patients with depression. Arthritis Res Ther 9:R48PubMedCrossRef
48.
go back to reference Kozora E, West SG, Maier SF, Filley CM, Arciniegas DB, Brown M, Miller D, Grimm A, Zhang L (2010) Antibodies against N-methyl-D-aspartate receptors in patients with systemic lupus erythematosus without major neuropsychiatric syndromes. J Neurol Sci 295:87–91PubMedCrossRef Kozora E, West SG, Maier SF, Filley CM, Arciniegas DB, Brown M, Miller D, Grimm A, Zhang L (2010) Antibodies against N-methyl-D-aspartate receptors in patients with systemic lupus erythematosus without major neuropsychiatric syndromes. J Neurol Sci 295:87–91PubMedCrossRef
49.
go back to reference Lapteva L, Nowak M, Yarboro CH, Takada K, Roebuck-Spencer T, Weickert T, Bleiberg J, Rosenstein D, Pao M, Patronas N, Steele S, Manzano M, van der Veen JW, Lipsky PE, Marenco S, Wesley R, Volpe B, Diamond B, Illei GG (2006) Anti-N-methyl-d-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum 54:2505–2514PubMedCrossRef Lapteva L, Nowak M, Yarboro CH, Takada K, Roebuck-Spencer T, Weickert T, Bleiberg J, Rosenstein D, Pao M, Patronas N, Steele S, Manzano M, van der Veen JW, Lipsky PE, Marenco S, Wesley R, Volpe B, Diamond B, Illei GG (2006) Anti-N-methyl-d-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum 54:2505–2514PubMedCrossRef
50.
go back to reference Lau A, Tymianski M (2010) Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch 460:525–542PubMedCrossRef Lau A, Tymianski M (2010) Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch 460:525–542PubMedCrossRef
51.
go back to reference Martel MA, Wyllie DJ, Hardingham GE (2009) In developing hippocampal neurons, NR2B-containing N-methyl-d-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death. Neuroscience 158:334–343PubMedCrossRef Martel MA, Wyllie DJ, Hardingham GE (2009) In developing hippocampal neurons, NR2B-containing N-methyl-d-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death. Neuroscience 158:334–343PubMedCrossRef
52.
go back to reference Matus S, Burgos PV, Bravo-Zehnder M, Kraft R, Porras OH, Farias P, Barros LF, Torrealba F, Massardo L, Jacobelli S, Gonzalez A (2007) Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med 204:3221–3234PubMedCrossRef Matus S, Burgos PV, Bravo-Zehnder M, Kraft R, Porras OH, Farias P, Barros LF, Torrealba F, Massardo L, Jacobelli S, Gonzalez A (2007) Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med 204:3221–3234PubMedCrossRef
53.
go back to reference Mayer ML, Vyklicky L, Sernagor E (1989) A physiologist’s view of the N-methyl-d-Aspartate receptor: an allosteric ion channel with multiple regulatory sites. Drug Dev Res 17:263–280CrossRef Mayer ML, Vyklicky L, Sernagor E (1989) A physiologist’s view of the N-methyl-d-Aspartate receptor: an allosteric ion channel with multiple regulatory sites. Drug Dev Res 17:263–280CrossRef
54.
go back to reference McLaurin EY, Holliday SL, Williams P, Brey RL (2005) Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 64:297–303PubMedCrossRef McLaurin EY, Holliday SL, Williams P, Brey RL (2005) Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology 64:297–303PubMedCrossRef
55.
go back to reference McLean BN, Miller D, Thompson EJ (1995) Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behcet’s disease involving the nervous system. J Neurol Neurosurg Psychiatry 58:548–554PubMedCrossRef McLean BN, Miller D, Thompson EJ (1995) Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behcet’s disease involving the nervous system. J Neurol Neurosurg Psychiatry 58:548–554PubMedCrossRef
56.
go back to reference Menon S, Jameson-Shortall E, Newman SP, Hall-Craggs MR, Chinn R, Isenberg DA (1999) A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum 42:735–741PubMedCrossRef Menon S, Jameson-Shortall E, Newman SP, Hall-Craggs MR, Chinn R, Isenberg DA (1999) A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum 42:735–741PubMedCrossRef
57.
go back to reference Moore PM (1999) Neuropsychiatric systemic lupus erythematosus. In: LR G (ed) Systemic lupus erythematosus. Academic press, San Diego, pp 575–578 Moore PM (1999) Neuropsychiatric systemic lupus erythematosus. In: LR G (ed) Systemic lupus erythematosus. Academic press, San Diego, pp 575–578
58.
go back to reference Olazaran J, Lopez-Longo J, Cruz I, Bittini A, Carreno L (2009) Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates. Eur Neurol 62:49–55PubMedCrossRef Olazaran J, Lopez-Longo J, Cruz I, Bittini A, Carreno L (2009) Cognitive dysfunction in systemic lupus erythematosus: prevalence and correlates. Eur Neurol 62:49–55PubMedCrossRef
59.
go back to reference Omdal R, Brokstad K, Waterloo K, Koldingsnes W, Jonsson R, Mellgren SI (2005) Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol 12:392–398PubMedCrossRef Omdal R, Brokstad K, Waterloo K, Koldingsnes W, Jonsson R, Mellgren SI (2005) Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors. Eur J Neurol 12:392–398PubMedCrossRef
60.
go back to reference Ozawa S, Kamiya H, Tsuzuki K (1998) Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 54:581–618PubMedCrossRef Ozawa S, Kamiya H, Tsuzuki K (1998) Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 54:581–618PubMedCrossRef
61.
go back to reference Perez-Otano I, Schulteis CT, Contractor A, Lipton SA, Trimmer JS, Sucher NJ, Heinemann SF (2001) Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. J Neurosci 21:1228–1237PubMed Perez-Otano I, Schulteis CT, Contractor A, Lipton SA, Trimmer JS, Sucher NJ, Heinemann SF (2001) Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. J Neurosci 21:1228–1237PubMed
62.
go back to reference Petri M, Naqibuddin M, Carson KA, Wallace DJ, Weisman MH, Holliday SL, Sampedro M, Padilla PA, Brey RL (2010) Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus. J Rheumatol 37:2032–2038PubMedCrossRef Petri M, Naqibuddin M, Carson KA, Wallace DJ, Weisman MH, Holliday SL, Sampedro M, Padilla PA, Brey RL (2010) Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus. J Rheumatol 37:2032–2038PubMedCrossRef
63.
go back to reference Qi X, Inagaki K, Sobel RA, Mochly-Rosen D (2008) Sustained pharmacological inhibition of deltaPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats. J Clin Invest 118:173–182PubMed Qi X, Inagaki K, Sobel RA, Mochly-Rosen D (2008) Sustained pharmacological inhibition of deltaPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats. J Clin Invest 118:173–182PubMed
64.
go back to reference Rogoz Z, Skuza G, Maj J, Danysz W (2002) Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 42:1024–1030PubMedCrossRef Rogoz Z, Skuza G, Maj J, Danysz W (2002) Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 42:1024–1030PubMedCrossRef
65.
go back to reference Sheng M, Pak DT (2000) Ligand-gated ion channel interactions with cytoskeletal and signaling proteins. Annu Rev Physiol 62:755–778PubMedCrossRef Sheng M, Pak DT (2000) Ligand-gated ion channel interactions with cytoskeletal and signaling proteins. Annu Rev Physiol 62:755–778PubMedCrossRef
66.
go back to reference Shiozawa S, Kuroki Y, Kim M, Hirohata S, Ogino T (1992) Interferon-alpha in lupus psychosis. Arthritis Rheum 35:417–422PubMedCrossRef Shiozawa S, Kuroki Y, Kim M, Hirohata S, Ogino T (1992) Interferon-alpha in lupus psychosis. Arthritis Rheum 35:417–422PubMedCrossRef
67.
go back to reference Sorrells SF, Caso JR, Munhoz CD, Sapolsky RM (2009) The stressed CNS: when glucocorticoids aggravate inflammation. Neuron 64:33–39PubMedCrossRef Sorrells SF, Caso JR, Munhoz CD, Sapolsky RM (2009) The stressed CNS: when glucocorticoids aggravate inflammation. Neuron 64:33–39PubMedCrossRef
68.
go back to reference Stahl-Hallengren C, Jonsen A, Nived O, Sturfelt G (2000) Incidence studies of systemic lupus erythematosus in Southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis. J Rheumatol 27:685–691PubMed Stahl-Hallengren C, Jonsen A, Nived O, Sturfelt G (2000) Incidence studies of systemic lupus erythematosus in Southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis. J Rheumatol 27:685–691PubMed
69.
go back to reference Steup-Beekman G, Steens S, van Buchem M, Huizinga T (2007) Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives. Lupus 16:329–334PubMedCrossRef Steup-Beekman G, Steens S, van Buchem M, Huizinga T (2007) Anti-NMDA receptor autoantibodies in patients with systemic lupus erythematosus and their first-degree relatives. Lupus 16:329–334PubMedCrossRef
70.
go back to reference Svenungsson E, Andersson M, Brundin L, van Vollenhoven R, Khademi M, Tarkowski A, Greitz D, Dahlstrom M, Lundberg I, Klareskog L, Olsson T (2001) Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus. Ann Rheum Dis 60:372–379PubMedCrossRef Svenungsson E, Andersson M, Brundin L, van Vollenhoven R, Khademi M, Tarkowski A, Greitz D, Dahlstrom M, Lundberg I, Klareskog L, Olsson T (2001) Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus. Ann Rheum Dis 60:372–379PubMedCrossRef
71.
go back to reference Trysberg E, Nylen K, Rosengren LE, Tarkowski A (2003) Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum 48:2881–2887PubMedCrossRef Trysberg E, Nylen K, Rosengren LE, Tarkowski A (2003) Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum 48:2881–2887PubMedCrossRef
72.
go back to reference Tymianski M, Charlton MP, Carlen PL, Tator CH (1993) Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons. J Neurosci 13:2085–2104PubMed Tymianski M, Charlton MP, Carlen PL, Tator CH (1993) Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons. J Neurosci 13:2085–2104PubMed
73.
go back to reference Utset TO, Fink J, Doninger NA (2006) Prevalence of neurocognitive dysfunction and other clinical manifestations in disabled patients with systemic lupus erythematosus. J Rheumatol 33:531–538PubMed Utset TO, Fink J, Doninger NA (2006) Prevalence of neurocognitive dysfunction and other clinical manifestations in disabled patients with systemic lupus erythematosus. J Rheumatol 33:531–538PubMed
74.
go back to reference Waterloo K, Omdal R, Husby G, Mellgren SI (2002) Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford) 41:411–415CrossRef Waterloo K, Omdal R, Husby G, Mellgren SI (2002) Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford) 41:411–415CrossRef
75.
go back to reference Waterloo K, Omdal R, Sjoholm H, Koldingsnes W, Jacobsen EA, Sundsfjord JA, Husby G, Mellgren SI (2001) Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J Neurol 248:595–602PubMedCrossRef Waterloo K, Omdal R, Sjoholm H, Koldingsnes W, Jacobsen EA, Sundsfjord JA, Husby G, Mellgren SI (2001) Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. J Neurol 248:595–602PubMedCrossRef
76.
go back to reference West SG, Emlen W, Wener MH, Kotzin BL (1995) Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic tests. Am J Med 99:153–163PubMedCrossRef West SG, Emlen W, Wener MH, Kotzin BL (1995) Neuropsychiatric lupus erythematosus: a 10-year prospective study on the value of diagnostic tests. Am J Med 99:153–163PubMedCrossRef
77.
go back to reference Winfield JB, Shaw M, Silverman LM, Eisenberg RA, Wilson HA 3rd, Koffler D (1983) Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med 74:837–844PubMedCrossRef Winfield JB, Shaw M, Silverman LM, Eisenberg RA, Wilson HA 3rd, Koffler D (1983) Intrathecal IgG synthesis and blood-brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med 74:837–844PubMedCrossRef
78.
go back to reference Yoshio T, Hirata D, Onda K, Nara H, Minota S (2005) Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus. J Rheumatol 32:34–39PubMed Yoshio T, Hirata D, Onda K, Nara H, Minota S (2005) Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus. J Rheumatol 32:34–39PubMed
79.
go back to reference Yoshio T, Onda K, Nara H, Minota S (2006) Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 54:675–678PubMedCrossRef Yoshio T, Onda K, Nara H, Minota S (2006) Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 54:675–678PubMedCrossRef
Metadata
Title
Systemic lupus erythematosus, the brain, and anti-NR2 antibodies
Authors
Maria B. Lauvsnes
Roald Omdal
Publication date
01-04-2012
Publisher
Springer-Verlag
Published in
Journal of Neurology / Issue 4/2012
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-011-6232-5

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