SEGREGATION OF PANCA ANTIGENIC RECOGNITION BY DNASE TREATMENT OF NEUTROPHILS - ULCERATIVE-COLITIS, TYPE-1 AUTOIMMUNE HEPATITIS, AND PRIMARYSCLEROSING CHOLANGITIS

Antineutrophil cytoplasmic antibodies (ANCA) have been identified in t he serum of 50-80% of ulcerative colitis (UC) patients. UC-associated ANCA yield a perinuclear staining pattern (pANCA) with alcohol-fixed n eutrophils. More recently, pANCA have been detected in the serum of pa tients with primary sclerosing cholangitis (PSC) and other autoimmune liver diseases. Up to 70% of PSC patient sera and up to 92% of sera fr om patients with well-defined type I autoimmune hepatitis (type 1 AM) were found to express pANCA. Such expression by patients with PSC and type 1 AIH raises questions concerning the relationship of these pANCA to each other and to that of UC. Differences and similarities in pANC A characteristics are found among the three diseases, suggesting the u se of pANCA to define specific disease subgroups. Our recent finding t hat the UC-associated pANCA reactive antigen was localized within the nuclear domain prompted an examination of whether DNase treatment of n eutrophils would alter antigenic recognition by the pANCA of UC, PSC, and type 1 AIH. While loss of antigenic recognition after DNase digest ion of neutrophils was a dominant feature of the UC-associated pANCA, the majority of PSC and type 1 AIH pANCA recognized cytoplasmic consti tuents. These results further support the feasibility of defining and/ or distinguishing disease subgroups based on the characterization of r espective pANCA.