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

https://doi.org/10.1074/mcp.M110.005330Get rights and content
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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 chromatography-tandem mass spectrometry shotgun analysis. The presence of serum IgG autoantibodies against 11 selected recombinant antigens was assessed by Western blot and enzyme-linked 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 αB (p = 0.0002), esterase D (p = 0.0002), APEX nuclease 1 (p < 0.0001), ribosomal protein P0 (p < 0.0001), and PA28γ (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.

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*This study was supported by a grant from the Health and Labor Sciences Research, Japan.

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The abbreviations used are:

    SLE

    systemic lupus erythematosus

    CNS

    central nervous system

    NP

    neuropsychiatric

    ACR

    American College of Rheumatology

    RA

    rheumatoid arthritis

    SSc

    systemic sclerosis

    SS

    Sjögren syndrome

    MS

    multiple sclerosis

    WB

    western blot

    HRP

    horseradish peroxidase

    NHC

    normal healthy control

    PBS

    phosphate buffered saline.