Diagnostic accuracy of four different immunological methods for the detection of anti-F-actin autoantibodies in type 1 autoimmune hepatitis and other liver-related disorders

Abstract

Background: Smooth muscle antibodies (SMA) with anti-F-actin specificity are commonly regarded as specific markers of type 1 autoimmune hepatitis (AIH-1) but, at the moment, a gold standard method for their identification is not available.

Objectives: To evaluate the diagnostic accuracy for AIH-1 of three new methods of detecting anti-F-actin antibodies, and to compare the results with those obtained using the indirect immunofluorescence (IIF) method on rodent tissue.

Methods: The sera of 33 AIH-1 patients and 104 controls (eight with type 2 AIH, 30 with chronic hepatitis C, 16 with celiac disease, 40 with primary biliary cirrhosis, and 10 with liver steatosis) were assayed for anti-F-actin antibodies using four methods: two IIF methods (one on rat tissue sections and the other on VSM 47 cell line derived from the thoracic aorta of rat embryo), an ELISA method and an Immunodot (ID) method.

Results: The diagnostic sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 51.5, 95.2, 77.3 and 86.1% for IIF on the VSM 47 cell line; 63.6, 86.5, 60 and 88.2% for the ELISA method; 72.7, 82.7, 57.1 and 90.5% for the ID assay; and 57.6, 96.1, 82.6 and 87.7% for the IIF on rat tissue sections.

Conclusion: The methods used for anti-F-actin antibody detection have different diagnostic performances. Both IIF methods, the one on rat tissues and the other on VSM47 cell line, are highly specific for AIH-1. In contrast, ELISA and especially ID show positive results in control population, although usually at low levels (with the single exception of PBC patients). Therefore, having a high positive predictive value, both IIF methods are reliable tools for the specific detection of AIH-associated anti-F-actin autoantibodies, whereas the immunometric assays might be integrated into the diagnostic scheme as second level tests upon improvement of their respective cut-offs to confirm anti-F-actin positivity in case of SMA positivity.