'True' antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both?

Clin Exp Immunol. 2004 Jan;135(1):154-8. doi: 10.1111/j.1365-2249.2004.02332.x.


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.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Blotting, Western / methods
  • Diagnosis, Differential
  • Enzyme-Linked Immunosorbent Assay / methods
  • False Negative Reactions
  • Female
  • Fluorescent Antibody Technique, Indirect / methods
  • Hepatitis, Autoimmune / diagnosis
  • Humans
  • Liver Cirrhosis, Biliary / diagnosis*
  • Liver Cirrhosis, Biliary / immunology
  • Male
  • Middle Aged
  • Mitochondria / immunology*
  • Sensitivity and Specificity


  • Autoantibodies
  • Biomarkers