ATYPICAL ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES WITH PERINUCLEAR FLUORESCENCE IN CHRONIC INFLAMMATORY BOWEL DISEASES AND HEPATOBILIARY DISORDERS COLOCALIZE WITH NUCLEAR LAMINA PROTEINS

Antineutrophil cytoplasmic antibodies (ANCA) are frequently associated with chronic inflammatory bowel diseases (IBD) and hepatobiliary diso rders, However their target antigens have not been identified yet. Rec ently, we observed an atypical perinuclear ANCA fluorescence (p-ANCA) together with an intranuclear staining using ANCA-positive sera from p atients with IBD and hepatobiliary disorders. This observation suggest s that the target antigens are localized within the nucleus of neutrop hilic granulocytes. To further investigate this hypothesis, we examine d sera from patients with ulcerative colitis, primary sclerosing chola ngitis, autoimmune hepatitis or systemic vasculitis on ethanol or form aldehyde-fixed neutrophils using confocal laser scanning microscopy an d immunoelectron microscopy. Counterstaining with propidium iodide, a DNA-specific dye, showed that ANCA-positive sera in IBD and heptobilia ry disorders react with intranuclear antigens at the nuclear periphery of the neutrophils. Double immunolabeling techniques revealed that nu clear lamina proteins, lamins A, C and B1, and lamin B receptor were c olocalized with the antigen(s) recognized by atypical p-ANCA, No coloc alization was observed with classical p-ANCA and antibodies against hi stones (H1-H4). Our study showed that atypical p-ANCA are antinuclear antibodies reactive with granulocyte-specific antigens present in the nuclear lamina.