Antibodies to smooth muscle

Autoimmune Hepatitis type 1 test.

Detection of anti-smooth muscle antibodies is used in the diagnosis of autoimmune Hepatitis. Anti-smooth muscle antibodies (ASMA) react with myofilaments in the cytoplasm of smooth muscle cells, the major one being fibrillarin (F-actin). There are several types of anti-smooth muscle antibodies, including fibrillar (F-) actin, tubulin, and desmin. Among them, only anti-F-actin antibodies are an autoimmune Hepatitis marker, while antibodies to tubulin, desmin and vimentin are detected 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 polymerised fibrillar (F-) forms. Autoantibodies in autoimmune Hepatitis react only with the F form of this protein. Autoantibody fixation is dependent on epitope conformation, so F-actin responce in native form is difficult. Therefore, the main method for detecting anti-F-actin antibodies is indirect immunofluorescence, which maximises the preservation of the autoantigen.

Anti-smooth muscle antibodies by immunofluorescence were first detected in chronic active Hepatitis patients (Johnson et al., 1965); this type of Hepatitis was subsequently termed autoimmune Hepatitis. Anti-smooth muscle antibodies directed against F-actin are considered the most sensitive marker of autoimmune Hepatitis type 1, although their degree of incidence in this disease is only 50-70%. In most cases, anti-smooth muscle antibodies are detected together with antinuclear factor on HEp-2 cell line. Anti-smooth muscle antibodies may be detected in primary biliary cirrhosis in 10% of cases. IgA anti-smooth muscle antibodies are often detected in celiac disease patients. Anti-smooth muscle antibodies are almost never detected, when associated with viral Hepatitis.

The serum of autoimmune Hepatitis type 1 patients (chronic active Hepatitis) reveals anti-smooth muscle antibodies, antinuclear factor on the НЕр2 cell line and high levels of gamma globulins, predominantly 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 autoimmune Hepatitis serological markers is included in the current criteria for this disease of the International Autoimmune Hepatitis Group 2008. The detection of any of these markers in high titre (≥1/80) combined with high hypergammaglobulinaemia 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 anti-asialoglycoprotein receptor (ASGPR) antibodies, which are noted at disease onset and their concentration increases with disease flare.