Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach

Lefranc, Didier; Launay, David; Dubucquoi, Sylvain; Seze, J. de; Dussart, Patricia; Vermersch, Marie; Hachulla, É.; Hatron, Pierre‐Yves; Vermersch, Patrick; Mouthon, Luc; Prin, Lionel

doi:10.1002/art.22863

Cited by 51 publications

(47 citation statements)

References 52 publications

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“…For example, a few brain antigenic targets were characterized in NPSLE patients using MALDI-TOF/MS analysis (10). However, only very small numbers of samples were analyzed in these studies, and larger validation studies are needed to establish the clinical relevance of these markers and their suitability for clinical assay development (9).…”

Section: Discussionmentioning

confidence: 99%

Identification of Three New Autoantibodies Associated with Systemic Lupus Erythematosus Using Two Proteomic Approaches

Katsumata

Kawaguchi

Baba

et al. 2011

Molecular & Cellular Proteomics

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Our objective was to identify new serum autoantibodies associated with systemic lupus erythematosus (SLE), focusing on those found in patients with central nervous system (CNS) syndromes. Autoantigens in human brain proteins were screened by multiple proteomic analyses: two-dimensional polyacrylamide gel electrophoresis/Western blots followed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry analysis and immunoprecipitation followed by liquid chromatographytandem mass spectrometry shotgun analysis. The presence of serum IgG autoantibodies against 11 selected recombinant antigens was assessed by Western blot and enzymelinked immunosorbent assay (ELISA) in the sera of 106 SLE patients and 100 normal healthy controls. The O.D. values in sera from SLE patients were significantly higher than those of controls for the antigens crystallin ␣B (p ‫؍‬ 0.0002), esterase D (p ‫؍‬ 0.0002), APEX nuclease 1 (p < 0.0001), ribosomal protein P0 (p < 0.0001), and PA28␥ (p ‫؍‬ 0.0005); the first three are newly reported. The anti-esterase D antibody levels were significantly higher in the CNS group than in the non-CNS group (p ‫؍‬ 0.016). Moreover, when the SLE patients were categorized using CNS manifestations indicating neurologic or psychiatric disorders, the anti-APEX nuclease 1 antibody levels were significantly elevated in SLE patients with psychiatric disorders (p ‫؍‬ 0.037). In conclusion, the association of SLE with several new and previously reported autoantibodies has been demonstrated. Statistically significant associations between anti-esterase D antibodies and CNS syndromes as well as between anti-APEX nuclease 1 antibodies and psychiatric disorders in SLE were also demonstrated. The combined immunoproteomic approaches used in this study are reliable and effective methods for identifying SLE autoantigens. Molecular &

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Section: Discussionmentioning

confidence: 99%

Identification of Three New Autoantibodies Associated with Systemic Lupus Erythematosus Using Two Proteomic Approaches

Katsumata

Kawaguchi

Baba

et al. 2011

Molecular & Cellular Proteomics

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“…More importantly, our current characterization of brain antigens matches more recent clinical reports on antibodies to the cytoskeletal protein MAP-2 (microtubule-associated protein-2) in NP SLE patients. 40,41 However, whether anti-cytoskeletal antibodies are indeed a novel class of pathogenic BRA requires further in vivo studies in which purified antibodies to different components of the cytoskeleton are centrally administered and behavioral outcomes carefully measured.…”

Section: Discussionmentioning

confidence: 99%

Autoimmunity as a principal pathogenic factor in the refined model of neuropsychiatric lupus

Loheswaran

Stanojcic

et al. 2010

Clinical & Exp Neuroim

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Objectives: Over the past decades, the MRL mouse model had shown significant validity in elucidating the pathogenesis of neuropsychiatric lupus erythematosus (NP SLE). However, the possibility that the inherited Fas receptor deficiency (and not autoimmunity) accounts for central nervous system (CNS) damage in the original stock 485 of MRL/MpJ‐Faslpr mice could not be rejected. The aim of the present study was to examine the consequences of autoimmune disease on behavior and brain morphology, while controlling for the genetic deficiency with a new, less symptomatic 6825 stock.Methods: Spleen mass, serum autoantibody and cytokine levels, immunoglobulins in cerebrospinal fluid (CSF), and brain planimetry were used to assess disease severity and CNS involvement in 5‐month‐old mice from stocks 6825 and 485. Their behavioral profiles were compared in a standard battery of tasks. The 2D‐DIGE and mass spectrometry examined brain antigens targeted by autoantibodies from serum and CSF.Results: The 6825 mice had smaller spleens, lower antibody and cytokine levels, and less IgG in the CSF. They were more active and showed better performance in tasks reflective of anxiety and motivated behavior. Signs of brain pathology were less profound and their CSF autoantibodies showed reduced affinity for brain antigens, largely characterized as highly‐conserved cytoskeletal proteins.Conclusions: The constellation of differences between the two MRL/MpJ‐Faslpr stocks confirms that the lpr mutation per se does not account for the brain pathology and altered behavior in the 485 stock. Together with significant correlations between immunological and behavioral measures, this observation suggests that soluble immune factors play a key role in pathogenesis of NP SLE. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2010.00014.x, September 2010)

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“…More specifically, 76.5% (13/17) of NPSLE patients were anti-MAP-2 positive [70]. By applying an immunoproteomic approach, MAP-2B proteins were noted to be preferentially recognized by sera from NPSLE patients, further suggesting this association [71].…”

Section: Microtubule-associated Protein 2 (Map-2) Antibodiesmentioning

confidence: 97%

Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers

Efthimiou

Blanco²

2009

Mod Rheumatol

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Systemic lupus erythematosus is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. In this article, we review the recent literature pertaining to the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We searched the PUBMED database with no chronological constraints using the following terms: "neuropsychiatric systemic lupus erythematosus" cross-referenced with the terms "pathogenesis" and "biomarkers" for full-text articles in English. The etiology of NPSLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. Of the numerous autoantibodies and biomarkers examined, anti-phospholipid, anti-ribosomal P, anti-neuronal, anti-glial fibrillary acidic protein (GFAP), anti-endothelial cell, anti-N-methyl-D: -aspartate (NMDA), microtubule-associated protein 2 (MAP-2), and matrix metalloproteinase-9 (MMP-9) appear to be elevated in patients with NPSLE. Cytokines that may be involved in the pathology of NPSLE include interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and interferons (IFN)-alpha and -gamma. With continued advances in immunological research, new insights into the pathophysiologic mechanisms of NPSLE may lead to the development of biomarkers and new treatment strategies.

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Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach

Cited by 51 publications

References 52 publications

Identification of Three New Autoantibodies Associated with Systemic Lupus Erythematosus Using Two Proteomic Approaches

Identification of Three New Autoantibodies Associated with Systemic Lupus Erythematosus Using Two Proteomic Approaches

Autoimmunity as a principal pathogenic factor in the refined model of neuropsychiatric lupus

Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers

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