Autoantibodies associated with neuropshychiatric systemic lupus erhytematosus

Main Article Content

Kazuhisa Nozawa



Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by damage to multiple organs caused by systemic autoimmunity. One of the characteristic features in SLE is the presence of numerous autoantibodies. Although certain autoantibodies such as anti-double strands DNA antibodies are known to be pathological, the correlation between many autoantibodies and tissue damage in patients with SLE remains unclear. Although the prognosis for survival in patients with SLE has improved dramatically in recent decades, its neuropsychiatric complications remain a major cause of morbidity. The neuropsychiatric manifestations can be attributed to SLE itself and are referred to as neuropsychiatric SLE (NPSLE). Multiple factors are involved in the pathogenesis of NPSLE including the genetic background, vasoculopathy, autoantibodies, and inflammatory mediators associated with SLE. However, neuropsychiatric manifestations can also be caused by other factors not associated with SLE, including steroid psychosis, infectious diseases, and metabolic factors. Therefore, NPLSE can be diagnosed in patients with SLE only if other causes have been excluded; difficulty in diagnosing NPSLE often occurs in many cases.

Various potential biomarkers for the diagnosis of NPSLE have been reported. However, useful and practical diagnostic biomarkers with high specificity for NPSLE have not been established to date. This review summarized the current data on autoantibodies recognized in NPSLE, and described their diagnostic value and pathogenic roles.

Article Details

How to Cite
NOZAWA, Kazuhisa. Autoantibodies associated with neuropshychiatric systemic lupus erhytematosus. Medical Research Archives, [S.l.], v. 5, n. Issue 9, sep. 2017. ISSN 2375-1924. Available at: <>. Date accessed: 25 mar. 2023.
autoantibody, systemic autoimmune disease, neuropshychiatric systemic lupus erhytematosus
Research Articles


1. Ruiz-Irastorza G, Khamashta MA, Castellino G, Hughes GR. Systemic lupus erythematosus. Lancet. 2001;357(9261):1027—1032.
2. Bresnihan B, Hohmeister R, Cutting J, Travers RL, Waldburger M, Black C et al. The neuropsychiatric disorder in systemic lupus erythematosus: evidence for both vascular and immune mechanisms. Ann Rheum Dis. 1979;38(4):301-306.
3. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82(5):299-308.
4. Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007;56(1):265-273.
5. [No authors listed]. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42(4):599-608.
6. Bertsias GK, Ioannidis JP, Aringer M, Bollen E, Bombardieri S, Bruce IN, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis. 2010;69(12):2074-2082.
7. Steup-Beekman GM, Zirkzee EJ, Cohen D, Gahrmann BM, Emmer BJ, Steens SC, et al. Neuropsychiatric manifestations in patients with systemic lupus erythematosus: epidemiology and radiology pointing to an immune-mediated cause. Ann Rheum Dis. 2013;72 Suppl 2:ii76-ii79.
8. Birnbaum J, Petri M, Thompson R, Izbudak I, Kerr D. Distinct subtypes of myelitis in systemic lupus erythematosus. Arthritis Rheum. 2009;60(11):3378-3387.
9. Barber CE, Leclerc R, Gladman DD, Urowitz MB, Fortin PR. Posterior reversible encephalopathy syndrome: an emerging disease manifestation in systemic lupus erythematosus. Semin Arthritis Rheum. 2011;41(3):353-363.
10. Yoshio T, Onda K, Nara H, Minota S. Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2006;54(2):675-678.
11. Hanly JG, Robichaud J, Fisk JD. Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. J Rheumatol. 2006;33(8):1553-1558.
12. Herranz MT, Rivier G, Khamashta MA, Blaser KU, Hughes GR. Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus. Arthritis Rheum. 1994;37(4):568-571.
13. Doe K, Nozawa K, Hiruma K, Yamada Y, Matsuki Y, Nakano S, et al. Antibody against chromatin assembly factor-1 is a novel autoantibody specifically recognized in systemic lupus erythematosus. Lupus. 2014;23(10):1031-1041.
14. Yamada Y, Nozawa K, Nakano S, Mitsuo Y, Hiruma K, Doe K, et al. Antibodies to microtubule-associated protein-2 in the cerebrospinal fluid are a useful diagnostic biomarker for neuropsychiatric systemic lupus erythematosus. Mod Rheumatol. 2016;26(4):562-568.
15. Banks WA, Erickson MA. The blood-brain barrier and immune function and dysfunction. Neurobiol Dis. 2010;37(1):26-32.
16. Ward PA. The dark side of C5a in sepsis. Nat Rev Immunol. 2004;4(2):133-142.
17. Negrini S, Pappalardo F, Murdaca G, Indiveri F, Puppo F. The antiphospholipid syndrome: from pathophysiology to treatment. Clin Exp Med. 2016 Jun 22. [Epub ahead of print].
18. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
19. Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun. 2000;15(2):145-151.
20. Mok CC, Lau CS, Wong RW. Neuropsychiatric manifestations and their clinical associations in southern Chinese patients with systemic lupus erythematosus. J Rheumatol. 2001;28(4):766-771.
21. Afeltra A, Garzia P, Mitterhofer AP, Vadacca M, Galluzzo S, Del Porto F, et al. Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies. Neurology. 2003;61(1):108-110.
22. Sanna G, Bertolaccini ML, Cuadrado MJ, Laing H, Khamashta MA, Mathieu A, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003;30(5):985-992.
23. Sciascia S, Bertolaccini ML, Roccatello D, Khamashta MA, Sanna G. Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review. J Neurol. 2014;261(9):1706-1714.
24. Elkon KB, Parnassa AP, Foster CL. Lupus autoantibodies target ribosomal P proteins. J Exp Med. 1985;162(2):459-471.
25. Bonfa E, Golombek SJ, Kaufman LD, Skelly S, Weissbach H, Brot N,et al. Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med. 1987;317(5):265-271.
26. Press J, Palayew K, Laxer RM, Elkon K, Eddy A, Rakoff D, et al. Antiribosomal P antibodies in pediatric patients with systemic lupus erythematosus and psychosis. Arthritis Rheum. 1996;39(4):671-676.
27. Karassa FB, Afeltra A, Ambrozic A, Chang DM, De Keyser F, Doria A, et al. Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum. 2006;54(1):312-324.
28. Hirohata S, Arinuma Y, Takayama M, Yoshio T. Association of cerebrospinal fluid anti-ribosomal p protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther. 2007;9(3):R44.
29. Toubi E, Shoenfeld Y. Clinical and biological aspects of anti-P-ribosomal protein autoantibodies. Autoimmun Rev. 2007;6(3):119-125.
30. Katzav A, Solodeev I, Brodsky O, Chapman J, Pick CG, Blank M, et al. Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system. Arthritis Rheum. 2007;56(3):938-948.
31. Matus S, Burgos PV, Bravo-Zehnder M, Kraft R, Porras OH, Farías P, et al. Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med. 2007;204(13):3221-3234.
32. DeGiorgio LA, Konstantinov KN, Lee SC, Hardin JA, Volpe BT, Diamond B. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med. 2001;7(11):1189-1193.
33. Lapteva L, Nowak M, Yarboro CH, Takada K, Roebuck-Spencer T, Weickert T, et al. Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum. 2006;54(8):2505-2514.
34. Hirohata S, Arinuma Y, Yanagida T, Yoshio T. Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther. 2014;16(2):R77.
35. Kowal C, DeGiorgio LA, Nakaoka T, Hetherington H, Huerta PT, Diamond B, et al. Cognition and immunity; antibody impairs memory. Immunity. 2004;21(2):179-188.
36. Sato T, Fujii T, Yokoyama T, Fujita Y, Imura Y, Yukawa N, et al. Anti-U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease. Arthritis Rheum. 2010;62(12):3730-3740.
37. Conti F, Alessandri C, Bompane D, Bombardieri M, Spinelli FR, Rusconi AC, et al. Autoantibody profile in systemic lupus erythematosus with psychiatric manifestations: a role for anti-endothelial-cell antibodies. Arthritis Res Ther. 2004;6(4):R366-R372.
38. Smith S, Stillman B. Immunological characterization of chromatin assembly factor I, a human cell factor required for chromatin assembly during DNA replication in vitro. J Biol Chem. 199125;266(18):12041-12047.
39. Williams RC Jr, Sugiura K, Tan EM. Antibodies to microtubule-associated protein 2 in patients with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2004;50(4):1239-1247.