Clinical correlation of antimitochondrial antibodies

Antimitochondrial antibodies (AMA) are a hallmark of primary biliary cirrhosis (PBC). They are believed to be absolutely disease specific. It does occur that patients with positive AMA are diagnosed with PBC in the absence of liver specific signs and symptoms. The aim of the present study was to examine the disease spectrum of unselected AMA positive patients of an university hospital.

All of the AMA tests performed in the immunological laboratory of the hospital between 1992 and 1998 were examined for positivity. 100 patients with a positive result were analyzed retrospectively for diagnosis, clinical and laboratory features.

61 patients suffered from liver diseases and 39 from non-liver diseases. The patients with liver diseases were 36 patients with PBC, 2 patients with PBC/PSC-overlap syndrome, 4 patients with autoimmune hepatitis and 19 patients with different liver diseases of other than autoimmune origin. The 39 patients with non-liver diseases included 9 patients with systemic autoimmune diseases, 3 patients with organ-specific autoimmune diseases, 8 patients with carcinoma and 19 patients with different diseases. 97 patients had an ELISA test for antibodies to the mitochondrial antigen M2 performed in addition to the immunofluorescence test for AMA. 73 patients had positive values for anti-M2 antibodies and 24 patients had negative results. Anti-M2 antibody values were divided in negative, low (5-100 U/ml), medium (101-1000 U/ml), high (1001-10000 U/ml) and very high (>10000 U/ml). Very high and high anti-M2 values were present mainly in patients with PBC and some patients with other liver diseases, medium high and low values in patients with different disease groups. In this unselected patient population only one third of AMA positive patients had an established diagnosis of PBC, about 10% a diagnosis of a systemic autoimmune disease and 3 % had other organ-specific autoimmune diseases. It can be concluded that, although high titers of antibodies against M2 are present mainly in patients with PBC, medium high and low titers may be present in patients lacking symptoms of PBC.

Although there is the possibility that the patients will develop the disease in the future, the presence of AMA alone does not seem to be sufficient to establish a diagnosis of PBC in a patient population in which at a given time point only 38 % of AMA positive patients have the disease.