title: 'True' antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both?
abstract: Anti-mitochondrial antibody (AMA) is considered the serological hallmark of primary biliary cirrhosis (PBC), but may be missing in a proportion of these patients. We assessed sensitivity and specificity of the currently available techniques for AMA detection in a large series of PBC patients and controls, and analysed their clinical and immunological features according to the AMA status. By indirect immunofluorescence on rat tissue sections and HEp-2 cells, Western immunoblot with bovine submitochondrial particles, and two ELISAs with AMA-specific recombinant proteins, we evaluated the presence of AMA in 127 PBC patients, 166 patients with type 1 autoimmune hepatitis and 100 with non alcoholic fatty liver disease. In PBC patients Western immunoblot detects AMA significantly more often than indirect immunofluorescence on HEp-2 cells (85%versus 72%, P = 0.02) or rodent tissue sections (71%, P = 0.01); both ELISAs are only slightly less sensitive than Western immunoblot (81% and 78%). Ten patients with non alcoholic fatty liver disease were AMA-positive by indirect immunofluorescence, but none recognized AMA-specific epitopes in Western immunoblot or in ELISAs. Twelve patients with type 1 autoimmune hepatitis were AMA-positive by indirect immunofluorescence, but only 6 (3.6%) reacted by Western immunoblot and ELISAs. Western immunoblot or ELISA should be regarded as first-line assay for the detection of AMA. Up to 15% of PBC patients are consistently AMA-negative, yet they share the same clinical, biochemical and histological features of AMA-positive PBC. Detection of AMA in type 1 autoimmune hepatitis might identify a subset of patients at risk of developing a hepatitic/cholestatic syndrome.
authors.affiliation: Department of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum - University of Bologna, Bologna, Italy. paolomuratori@tin.it
authors.forename: P
authors.initials: P
authors.lastname: Muratori
authors.forename: L
authors.initials: L
authors.lastname: Muratori
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
authors.forename: A J
authors.initials: AJ
authors.lastname: Czaja
authors.forename: G
authors.initials: G
authors.lastname: Pappas
authors.forename: S
authors.initials: S
authors.lastname: MacCariello
authors.forename: A
authors.initials: A
authors.lastname: Granito
authors.forename: F
authors.initials: F
authors.lastname: Cassani
authors.forename: P
authors.initials: P
authors.lastname: Loria
authors.forename: M
authors.initials: M
authors.lastname: Lenzi
authors.forename: F B
authors.initials: FB
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western / Q000379:methods; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005188:False Negative Reactions; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D019693:Hepatitis, Autoimmune / Q000175:diagnosis; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D015415:Biomarkers