PRIMARY BILIARY CIRRHOSIS (PBC) is an autoimmune liver disease characterized by chronic progressive destruction of small intrahepatic Saracatinib manufacturer bile ducts. Antimitochondrial antibodies (AMA), which mainly target the different subunits of the pyruvate dehydrogenase complex (PDC), are detected in 90% of PBC patients. However,
the pathogenic role of AMA in PBC has not been elucidated. Data from recent studies have suggested that some patients with PBC carry autoantibodies directed against muscarinic acetylcholine receptors, especially M3 muscarinic acetylcholine receptor (M3R).[1, 2] To date, five subtypes of muscarinic acetylcholine receptors (M1R–M5R) have been identified, and M3R is expressed in biliary tracts as well as exocrine glands and smooth muscles. Therefore, anti-M3R antibodies may play an important role in the pathogenesis of PBC and explain the organ-specificity of PBC. In this regard, anti-M3R
antibodies are also detected in patients with Sjögren’s syndrome, which is an autoimmune disease often associated with PBC.[3-6] The purpose of this study was to clarify the presence, the potential use as a diagnostic marker and the clinical roles of anti-M3R antibodies in patients with PBC. SERUM SAMPLES WERE collected from 90 Japanese patients with PBC, 40 Japanese patients with chronic hepatitis C (CHC), 21 Japanese patients with non-alcoholic steatohepatitis (NASH), 10 Japanese patients with primary sclerosing cholangitis (PSC), 14 Japanese patients with obstructive jaundice, and 10 Japanese patients see more with drug-induced liver injury as disease controls, who had been followed up at the Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan. All patients with PBC satisfied the Japanese Ministry
of Health, Labor and Welfare criteria for the diagnosis of PBC described in the PBC Guideline 2011. In the criteria, patients who satisfy one of the following items are diagnosed with PBC: (i) pathological BCKDHA examination shows chronic non-suppurative destructive cholangitis (CNSDC) and laboratory data are compatible with PBC; (ii) positive AMA and pathological examination does not show CNSDC but are compatible with PBC; and (iii) although pathological examination is not performed, AMA is positive, and clinical course is compatible with PBC. We collected clinical data of these patients with PBC, including pathological stage, antinuclear antibody, anti-La antibody and anti-Ro antibody. Pathological staging was determined according to Sheuer’s classification for 77 patients with PBC for whom histological examination was performed. All patients with NASH were diagnosed based on liver biopsy in non-alcoholic drinkers. Clinical and serological features of these disease controls are summarized in Table 1. Serum samples were also collected from 42 healthy volunteers at University of Tsukuba as healthy controls (HC). Ages and sexes of these HC are also presented in Table 1.