The presence of serum antimitochondrial antibodies (AMA) is a highly specific indication of primary biliary cirrhosis (PBC).
The reference range of antimitochondrial antibody immunoassay is a titer less than 1:40 on enzyme immunoassay (EIA) and negative on indirect immunofluorescence (IF). 
The value definitions for serum antimitochondrial antibodies listed by the Mayo Medical Laboratory include negative as less than 0.1 units, borderline as 0.1-0.3 units, weakly positive as 0.4-0.9 units, and positive as 1 or more units.
Specifics for collection of antimitochondrial antibody (AMA) are as follows:
Container: Red-top tube (serum)
Specimen preparation: Transport minimum of 0.5 mL of serum to transport tube
Storage/transport temperature: Refrigerated at 2-8°C
Unacceptable conditions: Plasma
Stability (collection to initiation of testing [after separation from cells]): Ambient, 8 hours; refrigerated, 7 days
Primary biliary cirrhosis (PBC) is a progressive inflammatory liver disease characterized by autoimmune-mediated destruction of intrahepatic bile ducts. It primarily occurs among women aged 40-60 years.
Positive serum antimitochondrial antibody (AMA) result (titers >1:40)
Cholestatic pattern of liver enzymes for more than 6 months
Histopathologic evidence of asymmetric destruction of intrahepatic bile ducts
Serum antimitochondrial antibody targets non–organ-specific mitochondrial antigens numerically classified as M1-M9. M2 is the most commonly recognized antigen complex, consisting of 2-oxo-acid dehydrogenase complex (2-OADHC) family located in the inner mitochondrial membrane. 2-OADHC is composed of E1, E2, and E3 subunits, E2 being the immunodominant epitope targeted by antimitochondrial antibody-M2. One of the enzymes that belong to 2-OADHC is pyruvate dehydrogenase complex (PDC). A recombinant form of PDC is cloned and used to detect the presence of AMA in serum via EIA. 
Although immunofluorescence assay is an alternative testing method, EIA is preferred because of fewer technical challenges and greater reproducibility of the assay. 
Antimitochondrial antibody testing is usually obtained as part of a laboratory workup for patients with known or suspected hepatobiliary disease. This broad population of patients may present with a constellation of findings, including fatigue, pruritus, elevated levels of transaminases, increased alkaline phosphatase levels, and hyperbilirubinemia. In such a setting, laboratory tests for drug-induced hepatitis, metabolic disease, viral hepatitis, and various autoimmune diseases may also be obtained to assist in establishing the diagnosis.
Even among asymptomatic patients, a positive serum antimitochondrial antibody result is highly suggestive of primary biliary cirrhosis or indicates of significant risk of developing active primary biliary cirrhosis in succeeding years.  However, note that the quantitative measurement of antimitochondrial antibody does not reflect on progression of the disease nor carry any prognostic value.  In addition, 5%-10% of patients with primary biliary cirrhosis are reported to have no detectable level of serum antimitochondrial antibody. Nonetheless, these serologically negative patients follow the same clinical and histological features as seropositive patients. 
Among recipients of liver transplants for end-stage primary biliary cirrhosis, the serum antimitochondrial antibody level can decrease slightly and elevate back to pretransplant levels in the first year posttransplant.  However, this fluctuation does not reflect recurrence of the disease and offers no clinical significance.  In addition, a minority of patients with fulminant hepatic failure from various causes, such as drug-induced liver damage and hepatitis A and B, are reported to have transiently detectable levels of serum antimitochondrial antibody that disappear within one year. 
Some individuals with chronic graft versus host disease are reported to have detectable levels of antimitochondrial antibody because of a related pathogenic background. 
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Yoon Chul Shin St Louis University School of Medicine
Disclosure: Nothing to disclose.
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology
Disclosure: Nothing to disclose.
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