Clinical Information

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by the presence of diverse autoantibodies, increased concentrations of specific liver enzymes, hypergammaglobulinemia and abnormalities in liver histology.(1-3) AIH affects all ages and races and is categorized into type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is by far more common and affects both children and adults, whereas AIH-2 is mainly a pediatric disease.(3,4) AIH-1 is characterized by positive anti-nuclear antibody (ANA) and/or anti-smooth muscle antibody (SMA), whereas AIH-2 is characterized by positive anti-liver kidney microsomal antibody type 1 (LMK-1) and/or anti-liver cytosol type 1 antibodies.(3,4) Anti-soluble liver antigen (anti-SLA) antibody, a disease-specific autoantibody, is seen in both AIH-1 and AIH-2, a feature that, coupled with its high disease specificity, suggests a key pathophysiological role of its antigenic target in the disease process.(3-5) Also referred to as anti-SLA/LP (liver-pancreas) antibody, it was originally identified by Manns M, et al in 1987(6) in patients HBsAg-negative chronic active hepatitis.(reviewed in 3) The SLA autoantibodies were subsequently identified as targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), a 56 kDa cytosolic protein of 501 amino acids detected in both AIH-1 and AIH-2 and are the only disease-specific AIH-associated autoantibody.(3,7)

Anti-soluble liver antigen (anti-SLA) antibody testing is recommended in American Association for the Study of Liver Diseases/International Autoimmune Hepatitis Group (AASLD/IAIHG) guidelines for AIH, especially for identifying patients with cryptogenic hepatitis with features of autoimmune disease.(1,2) Although they appear in only 20% to 30% of AIH or 10% to 30% in cryptogenic (unexplained) chronic hepatitis patients, they are crucial for diagnosis as they can be the sole marker in "seronegative" cases (negative for ANA/SMA).(3,5,8) Anti-SLA antibodies can also be detected in some patients with primary biliary cholangitis-AIH overlap syndrome.(3) In addition, some studies have noted that anti-SLA-positive patients might show lower serum aspartate aminotransferase (AST) levels and lower-globulins compared to ANA/SMA positive patients at diagnosis.(9) Anti-SLA antibodies are very specific for AIH, appearing rarely in healthy individuals and other non-hepatic autoimmune conditions.(3,8) In general, patients positive for anti-SLA antibodies appear to have clinical, histological, and laboratory features to non-SLA positive AIH-1 patients.(8) Although anti-SLA positivity has been reported to demonstrate a more aggressive clinical course, these results appear to be inconclusive.(3,5,9-11) Possibly due to the rarity of anti-SLA antibody-positive AIH patients, characteristics of disease cohorts, or type of assay used in these studies.(3,5,9-11) Therefore, it is likely the requirement of lifelong immunosuppression and/or higher relapse rates after treatment withdrawal would be based on patient-specific factors, test method, or clinician's judgment.

Detection of anti-SLA antibodies primarily relies on solid-phase immunoassays (SPAs) rather than traditional indirect immunofluorescence assay (IFA).(3-5,8-11) This is because the target antigen-a 50 kDa cytosolic protein identified as seryl-tRNA:selenocysteinyl-tRNA synthase-is soluble and lost during the preparation of standard tissue substrates used in immunofluorescence assays (IFA).(reviewed in 3) Of the SPAs, the enzyme-linked immunosorbent assay was the first method to be validated for use in an international study and is most widely used test.(8,9) The line immunoassay is also another commonly used method.(10) These typically use recombinant human SLA/LP antigen to provide a qualitative and/or semi-quantitative measure of IgG antibodies in patient serum.