IMMUNOREACTIVITY TO M2 PROTEINS IN ANTIMITOCHONDRIAL ANTIBODY-NEGATIVE PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS

Although antimitochondrial auto-antibodies are characteristically pres ent in the serum of patients with primary biliary cirrhosis (PBC), the re is a discrepancy between the positivity for antimitochondrial antib ody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreact ivity to four inner mitochondrial membrane proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There w ere no significant differences between the AMA-negative and AMA-positi ve groups in clinical characteristics or histologically determined dis ease stage. Immunoblot analysis showed that all patients had anti-M2 a uto-antibodies to one or more of the four M2 proteins. Nine (60%) of t he 15 AMA-negative patients had antibodies to only one M2 protein (eit her 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres (greater than or equal to 1 : 320) had antibodies to all fo ur M2 proteins. There was a significant rank correlation between the A MA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunog enicity of M2 proteins but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.