Antibodies to actin
A test to diagnose autoimmune hepatitis type 1.
The detection of smooth muscle antibodies is used in the diagnosis of autoimmune hepatitis. Smooth muscle antibodies (SMA) react with myofilaments in the cytoplasm of smooth muscle cells, the main one being fibrillarin (F-actin). There are several types of smooth muscle antibodies, including antibodies to fibrillar (F-) actin, tubulin, and desmin. Among them, only antibodies to F-actin are a marker of autoimmune hepatitis, while antibodies to tubulin, desmin and vimentin are found in rheumatic diseases and viral infections and have no independent clinical significance. Actin is a 46 kDa globular protein that makes up the bulk of eukaryotic cell microfilaments. Actin can exist in both monomeric (M-) and polymerized fibrillar (F-) forms. Autoantibodies in autoimmune hepatitis react only with the F-form of this protein. The binding of autoantibodies depends on the conformation of epitopes, so the isolation of F-actin in its native form is difficult. In this regard, the main method of detection of antibodies to F-actin is indirect immunofluorescence, which allows for maximum preservation of the autoantigen.
Smooth muscle antibodies by immunofluorescence were first identified in patients with chronic active hepatitis (Johnson et al., 1965), which was subsequently termed "autoimmune hepatitis". Smooth muscle antibodies directed against F-actin are considered to be the most sensitive marker of autoimmune hepatitis type 1, although their occurrence in this disease is only 50-70%. In most cases, they are detected together with antinuclear factor on HEp-2 cell line. In 10% of cases, smooth muscle antibodies may be observed in primary biliary cirrhosis. IgA class smooth muscle antibodies are often found in patients with celiac disease. Antibodies to smooth muscle are practically not found in the background of viral hepatitis.
The serum of patients with autoimmune hepatitis type 1 (chronic active hepatitis) reveals smooth muscle antibodies, antinuclear factor on the HER2 cell line and high levels of gamma globulins, mainly immunoglobulin IgG. In type 2 autoimmune hepatitis, antibodies to liver-kidney microsomes are detected. Finally, type 3 autoimmune hepatitis is accompanied by the appearance of antibodies to soluble hepatic antigen. The detection of these serologic markers of autoimmune hepatitis is included in the current criteria for this disease: International Autoimmune Hepatitis Study Group 2008. Detection of any of these markers in high titer (≥1/80) in combination with high hypergammaglobulinemia provides 4 of the 7 points required for a definitive diagnosis of autoimmune hepatitis. An important additional marker of autoimmune hepatitis is the detection of antibodies to the asialoglycoprotein receptor (ASGPR), which are noted at disease onset and their concentration increases with disease exacerbation.