Antimitochondrial and other autoantibodies Dimitrios-Petrou Bogdanos, MD a , Harold Baum, PhD b , Diego Vergani, PhD, MD, FRCPath, FRCP a, * a Institute of Liver Studies, King’s College Hospital, Denmark Hill Campus, London SE5 9RS, UK b Division of Life Sciences, King’s College London, Campden Hill Road, London W8 7AH, UK The nature of primary biliary cirrhosis (PBC), a disease first recognized by Addison and Gull in 1851, became clearer around the 1960s when first its apparent [1] and then its unequivocal association [2], with antimitochondrial antibody were described. In 1958, Mackay [1] reported a case of PBC with high titers of complement-fixing antibodies to tissue homogenates. Absorption studies showed that the antibody reactivity could be abolished using a mitochondrial fraction of rat liver [3]. A milestone for the clinical hepatologist was the observation in 1965 by Walker, Doniach, Roitt, and Sherlock [4] that antimitochondrial antibodies (AMAs) were present in all their patients with PBC and in none of the controls, which included patients with extrahepatic bile-duct obstruction, drug-induced cholestasis, and viral hepatitis. Ever since the description of this close association, AMAs have acted as a powerful diagnostic tool. Soon it became clear that positivity for AMAs was able to direct toward the correct diagnosis in the work-up of cholestatic conditions, at times avoiding invasive procedures such as explorative laparotomy. In addition to revealing a diagnostic marker, the paper by Walker et al [4] had two additional and connected merits: it showed what antimitochondrial reactivity looks like under a fluorescent microscope, and it provided a straightfor- ward technique for its detection. Almost 40 years on, detection of AMAs is rou- tinely done as first described in the laboratory of Professor Deborah Doniach [4,5]. In 1967, Berg et al [6] demonstrated that PBC sera reacted in vitro with isolated mitochondria, the antigen being later localized to the inner membrane [7]. New clinical studies confirmed the AMAs’ power in the diagnosis of PBC, whether it was tested by complement fixation [8] or by immunofluorescence [4,9]. PBC-specific AMAs were shown to react with trypsin-sensitive antigens, named as M2 antigens. This designation arose within an arbitrary classification system of 1089-3261/03/$ – see front matter D 2003 Elsevier Inc. All rights reserved. doi:10.1016/S1089-3261(03)00104-1 * Corresponding author. E-mail address: diego.vergani@kcl.ac.uk (D. Vergani). Clin Liver Dis 7 (2003) 759 – 777