Anti-mitochondrial antibodies: what’s new?

Abstract

<h3>Introduction</h3> The method of choice for anti-mitochondrial antibody detection has been indirect immunofluorescence (AMA-IIF) on fresh frozen sections of rodent liver, kidney and stomach with an accepted sensitivity of between 90 and 95%. However, primary biliary cirrhosis (PBC) is a disease of variable prognosis and up to now there have been no assays that have been able to predict patients who are more likely to progress to liver failure. Recently, a line blot assay has become available (EUROIMMUN) that utilises both native PDC and the recombinant ‘triple' E2 subunit antigen M2-3E in addition to PBC-specific anti-nuclear antigens (ANAs), gp210 (nuclear pore), Sp100 (multiple nuclear dots) and PML (promyelocytic leukaemia nuclear bodies). <h3>Aim</h3> To investigate the performance of this assay in identifying patients with clinical PBC and to investigate the performance of this assay in identifying patients who are more likely to progress to more severe PBC based on profiling reactivities to M2, M2-E3 and the PBC-specific ANAs. <h3>Patients</h3> Patients included 48 consecutive AMA-IIF positive patients detected during routine autoantibody investigation, 37 patients being followed up in specialist gastroenterology clinics for PBC and 49 patients receiving a liver transplant for PBC. <h3>Results</h3> A review of the available clinical, biochemical and biopsy data on the 48 consecutive AMA-IIF positive patients found that patients who were anti-M2 and anti-M2-E3 positive were more likely to have clinical PBC at the time of testing, <i>p</i> ≤ 0.005 compared to those who were anti-M2/M2-E3 negative. These results were confirmed when all three groups were compared. The frequency of anti-M2 and anti-M2-E3 positivity was significantly higher in the PBC transplant group, <i>p</i>=0.0025 compared to the two groups. The frequency of anti-gp210 was also significantly higher in the PBC transplant group, <i>p</i>=0.026, supporting previous reports that anti-gp210 appears to be a significant risk factor for hepatic failure in PBC patients. We also confirmed that anti-Sp100 positivity was not clinically important in PBC patients. However, the frequency of anti-PML positivity was higher in the PBC transplant group. <h3>Conclusion</h3> We conclude that testing for anti-M2, anti-E3, anti-gp210 and anti-PML may be useful in identifying PBC patients who are at greater risk of disease progression.