Atypical antineutrophil cytoplasmic antibodies with perinuclear fluorescence in chronic inflammatory bowel diseases and hepatobiliary disorders colocalize with nuclear lamina proteins

Authors

  • Birgit Terjung M.D.,

    Corresponding author
    1. Department of General Internal Medicine, Columbia University, New York, New York
    2. Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York
    • Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University 630 West 168th Street, P & S 10-508, New York, NY 10032. Fax: (212) 305-6443
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  • Volker Herzog,

    1. Institute of Cell Biology and Bonner Forum Biomedizin, University of Bonn, Bonn, Germany
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  • Howard J. Worman,

    1. Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York
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  • Ingo Gestmann,

    1. Institute of Cell Biology and Bonner Forum Biomedizin, University of Bonn, Bonn, Germany
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  • Christoph Bauer,

    1. Institute of Cell Biology and Bonner Forum Biomedizin, University of Bonn, Bonn, Germany
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  • Tilman Sauerbruch,

    1. Department of General Internal Medicine, Columbia University, New York, New York
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  • Ulrich Spengler

    1. Department of General Internal Medicine, Columbia University, New York, New York
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Abstract

Antineutrophil cytoplasmic antibodies (ANCA) are frequently associated with chronic inflammatory bowel diseases (IBD) and hepatobiliary disorders. However, their target antigens have not been identified yet. Recently, we observed an atypical perinuclear ANCA fluorescence (p-ANCA) together with an intranuclear staining using ANCA-positive sera from patients with IBD and hepatobiliary disorders. This observation suggests that the target antigens are localized within the nucleus of neutrophilic granulocytes. To further investigate this hypothesis, we examined sera from patients with ulcerative colitis, primary sclerosing cholangitis, autoimmune hepatitis or systemic vasculitis on ethanol or formaldehyde-fixed neutrophils using confocal laser scanning microscopy and immunoelectron microscopy. Counterstaining with propidium iodide, a DNA-specific dye, showed that ANCA-positive sera in IBD and heptobiliary disorders react with intranuclear antigens at the nuclear periphery of the neutrophils. Double immunolabeling techniques revealed that nuclear lamina proteins, lamins A, C and B1, and lamin B receptor were colocalized with the antigen(s) recognized by atypical p-ANCA. No colocalization was observed with classical p-ANCA and antibodies against histones (H1-H4). Our study showed that atypical p-ANCA are antinuclear antibodies reactive with granulocyte-specific antigens present in the nuclear lamina.

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