NUCLEAR-LOCALIZATION OF THE ANTIGEN DETECTED BY ULCERATIVE COLITIS-ASSOCIATED PERINUCLEAR ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES

Antineutrophil cytoplasmic antibodies (ANCAs) identified in the serum of 50 to 80% of ulcerative colitis (UC) patients yield a perinuclear s taining pattern (pANCA) with alcohol-fixed neutrophils. The ANCAs of U C are distinguishable from those described for Wegener's granulomatosi s and other vasculitidies. These various non-UC ANCAs recognize neutro phil granule constituents, but the antigenic moiety specific for the U C pANCA remains unknown. Although the perinuclear nature of some ANCA reactions is all artifact of the alcohol fixation of neutrophils, whic h causes cytoplasmic granules to redistribute around the nucleus, the UC pANCA reaction has been found not to be similarly affected We postu lated a nuclear localization for the UC-associated pANCA antigen and u sed both confocal laser microscopy and immunoelectron microscopy to ex amine the neutrophil reaction of UC-associated pANCA-containing sera. Confocal microscopy revealed a nuclear reaction for 88% (22/25) of the sera with 72% (18/25) showing the reaction localizing to the inner si de of the nuclear (membrane) periphery. Immunoelectron microscopy show ed that the UC-associated pANCA reaction localized primarily over chro matin concentrated toward the nuclear periphery, although the sera did not recognize doable-stranded DNA. These results confirm the nuclear localization of the UC-associated pANCA antigen.