Characterization and clinical relevance of a new complement-fixing antibod-anti-m8-in patients with primary biliary cirrhosis

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Abstract
A new complement-fixing antimitochondrial antibody-anti-M8-was detected in patients with primary biliary cirrhosis. Anti-M8 was only found in association with anti-M2, however, not all anti-M2 positive patients had anti-M8. Thus, among 66 anti-M2 positive patients, 29 were also positive for anti-M8, whereas sera from patients who had the complement-fixing anti-M2 and anti-M4 antibodies in parallel always strongly reacted with the M8 antigen. This group was previously described as mixed form. The M8 antigen was isolated either from human liver mitochondria or pig kidney microsomes and could be clearly distinguished from the M4 antigen. In contrast to M4, M8 was trypsin sensitive and banded at sucrose densities from 1.16 to 1.24, while M4 was found at densities from 1.08 to 1.14. Like M4, the M8 antigen also co-purified with outer mitochondrial membranes. Fifty-three patients with primary biliary cirrhosis have been followed over a period of up to 16 years and were classified according to their complement-fixing antimitochondrial antibody profile. At the time of the first diagnosis, 95% of 31 patients being anti-M2 positive, but anti-M8 negative (antimitochondrial antibody Profile I) were in Stage I or II. In contrast, only 61% of 13 patients being anti-M2 and anti-M8 positive (antimitochondrial antibody Profile II) and 44% of 9 patients with anti-M2, anti-M8 and anti-M4 in parallel (antimitochondrial antibody Profile III) belonged to Stage I or II. At the end of the observation period, only 24% of patients with antimitochondrial antibody Profile I (anti-M8 negative) had reached Stage III or IV, while 75% of patients with antimitochondrial antibody Profile II or III (anti-M8 positive) had a progression to Stage III or IV. It is concluded that the presence of complement-fixing anti-M8 antibody may herald a more progressive course of primary biliary cirrhosis.