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OP0215 Association of Cerebrospinal Fluid Anti-Sm Antibodies with Acute Confusional State in Systemic Lupus Erythematosus
  1. S. Hirohata1,
  2. T. Yanagida2,
  3. T. Yoshio3
  1. 1Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa
  2. 2Internal Medicine, Teikyo University School of Medicine, Tokyo
  3. 3Rheumatology and Clinical Immunology, Jichi Medical University, tochigi, Japan

Abstract

Background Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies disclosed the strong association between serum anti-Sm antibodies and organic brain syndrome, consisting mainly of acute confusional state (ACS) of diffuse NPSLE, although the mechanism remains unclear. On the other hand, recent studies revealed the elevation of cerebrospinal fluid (CSF) anti-RNP antibodies in NPSLE.

Objectives The current studies were carried out to explore the association of CSF anti-Sm with various subsets of NPSLE.

Methods Paired serum and CSF specimens were obtained from 72 patients with NPSLE (49 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE], 23 with neurological syndromes or peripheral neuropathy [focal NPSLE]) and from 22 control patients with non-SLE neurological diseases. Anti-Sm, anti-RNP and albumin in CSF and sera were measured by ELISA. Blood-brain barrier (BBB) function and intrathecal anti-Sm production were evaluated by Q albumin and CSF anti-Sm index, respectively. Binding of monoclonal anti-Sm to neuroblastoma cell lines SK-N-MC and Neuro2a was examined by flow cytometry.

Results Anti-Sm and anti-RNP in CSF and sera were elevated in NPSLE compared with non-SLE control. Among NPSLE, CSF anti-Sm, but not CSF anti-RNP, were significantly elevated in acute confusional state (ACS) compared with non-ACS diffuse NPSLE or with focal NP-SLE (figure). Whereas there were no significant differences in CSF anti-Sm index among the 3 groups of NPSLE, Q albumin and serum anti-Sm were elevated in ACS compared with non-ACS or with focal NPSLE. Notably, CSF anti-Sm was correlated with Q albumin (r=0.2373, p=0.0447) or more closely with serum anti-Sm (r=0.7185, p<0.0001) in 72 patients with NPSLE. Finally, monoclonal anti-Sm bound to the surface of neuroblastoma cell lines SK-N-MC and Neuro2a.

Conclusions These results indicate that anti-Sm are constituents of anti-neuronal antibodies. More importantly, the data demonstrate that the elevation of CSF anti-Sm through transudation from the systemic circulation, due to both damaged BBB and increased serum anti-Sm, plays a critical role in the pathogenesis of ACS.

References

  1. Hirohata S, Kosaka M. Association of anti-Sm antibodies with organic brain syndrome secondary to systemic lupus erythematosus. Lancet 1994; 343:796.

  2. 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: 3730-40.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.1677

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