The antimitochondrial antibody anti-M9. A marker for the diagnosis of early primary biliary cirrhosis

The clinical relevance of a new antimitochondrial antibody, anti-M9, reacting with an outer membrane-associated antigen on liver mitochondria is described. Sera from 22 anti-M2-negative patients with histologically proven primary biliary cirrhosis (PBC) who had been followed for 5-15 years were tested for anti-M9 in the ELISA using a purified M9-fraction. 18 (82%) were anti-M9-positive, and 17 of them (94%) were in stage I/II. None of the 17 anti-M9-positive/anti-M2-negative patients with early PBC progressed to stage III/IV during the observation period of 5-15 years, and in all instances anti-M9 remained of the IgM-type. In one anti-M9-positive patient anti-M2 of the IgM type appeared 2 years after the first demonstration of anti-M9. Among 156 patients with anti-M2-positive PBC, 58 (37%) had anti-M9, and 39 of them (67%) were in stage I/II. 19 of these 39 stage I/II patients (49%) had anti-M9 exclusively of the IgM-type in contrast to none of the 19 stage III/IV patients. Using the purified M9-fraction in ELISA and Western blotting, anti-M9 antibodies were confined only to patients with PBC or overlap syndromes between PBC and autoimmune chronic active hepatitis (10% of 133 patients) and were not found in patients with other hepatic and non-hepatic disorders. We conclude that the determination of anti-M9 may be helpful for the diagnosis of early and asymptomatic PBC. From follow-up studies of anti-M9-positive but anti-M2-negative patients it emerges that this antibody type may be associated with a benign course of PBC.