Primary biliary cholangitis (PBC) is an autoimmune disease of the liver. It is characterized by the chronic inflammatory destruction of intrahepatic bile ducts leading to cholestasis and cirrhosis. M2 antimitochondrial antibodies (AMA) are the serological hallmark of PBC and are found in 90%–98% of PBC patients. PBC-specific antinuclear antibodies, particularly anti-Gp210 and anti-Sp100, are used for the diagnosis of PBC in AMA-negative PBC patients and are included in the diagnosis criteria of PBC. Moreover, anti-Gp210 antibody has been associated with disease severity.
Gp210 is an integral membrane protein that anchors the nuclear pore complex to the nuclear membrane. It has a cytoplasmic carboxy-terminal domain, an amino-terminal domain located in the perinuclear space, and a transmembrane segment. The C-terminal tail domain comprises 58 amino acids. In PBC, the anti-Gp210 antibody recognizes an epitope, which is contained within a linear stretch of 15 amino acids within the C-terminal domain of the protein.
Sp100 is a nuclear protein of 480 amino acids with aberrant electrophoretic mobility to 100 kDa. One or more major autoreactive epitopes are localized in the carboxy-terminal half of Sp100. Anti-Sp100 antibodies from PBC patients recognize discontinuous or conformation-dependent epitopes.
It has been hypothesized that the frequency of PBC-specific antinuclear antibodies (anti-Gp210 and anti-Sp100) varies according to the ethnic origin of PBC patients. Furthermore, a significant genetic predisposition to have anti-Sp100, but not anti-Gp210 antibodies, has been demonstrated.