Autoantibodies are a defining feature of autoimmune hepatitis (AIH). They fall into the conventional antibodies used to support the diagnosis and a larger group of less common ones that refine the picture or mark a variant.
Conventional autoantibodies
The conventional antibodies investigated in AIH are anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA) and anti-LKM1.
ANA are screened by immunofluorescence, which reports the pattern of fluorescence — commonly homogeneous, sometimes heterogeneous — alongside the titre. Because the nuclear target antigens are unknown in at least a third of patients, a second and more specific line by ELISA tests individual reactivities such as anti-chromatin, anti-histone and anti-native DNA.
SMA with anti-actin activity are specific for AIH, and they carry prognostic weight as well as diagnostic weight: they are associated with an earlier age of onset, a poorer response to treatment and more deaths from liver damage. SMA positivity is also more common in patients with the HLA DR3-B8 profile.
Anti-LKM1 is the antibody that defines type 2 disease and is usually positive when both SMA and ANA are negative.
Testing the conventional antibodies together has a characteristic performance: positivity for both ANA and SMA has a sensitivity of less than 50% but a specificity of more than 99% for AIH. A positive result is therefore a strong clue to the diagnosis, but not definitive on its own.
Less common autoantibodies
Several other antibodies can be found in AIH.
Atypical perinuclear anti-neutrophil cytoplasmic antibodies (atypical pANCA) are common in type 1 disease but are not specific to AIH.
Antibodies to soluble liver antigen (anti-SLA) are the most disease-specific of the group. Patients who are positive mostly have severe disease and relapse when treatment is withdrawn, and about 15% of AIH patients in the US are positive.
Anti-actin antibodies are a subset of SMA; they are the reactivity that gives SMA its specificity for AIH.
Anti-LC1 is commonly found in patients who are also positive for anti-LKM1. These patients are mostly young — between 2 and 26 years of age — and more often have concurrent immune disorders such as vitiligo and diabetes mellitus (DM); they tend to progress to cirrhosis within 3 years of diagnosis.