Autoantibodies to asialoglycoprotein receptor (ASGPR) in patients with autoimmune liver diseases

• The ELISA with highly purified rabbit ASGPR can be used as a complementary test for autoimmune liver disease serology.
• The Anti-ASGPR ELISA is well suited for routine laboratories basing their Ab testing on solid-phase enzyme immunoassays.
• Individuals with clinical suspicion of AIH and seronegative conventional AIH-related Abs should to be screened for ASGPR Abs.
• ASGPR Abs can be found in patients with AIH as the only disease-related autoantibody.
• The high prevalence of ASGPR Abs in patients with PSC needs to be corroborated by further studies.

BackgroundThe liver asialoglycoprotein receptor (ASGPR) is the only organ-specific autoantigenic target in autoimmune hepatitis (AIH) patients and corresponding autoantibodies (Abs) have been suggested aiding in the serology of autoimmune liver diseases (ALD).MethodsA novel enzyme-linked immunosorbent assay (ELISA) employing purified rabbit ASGPR was used to detect ASGPR Abs in patients with ALD and controls. ASGPR Ab was determined in sera from 172 patients with AIH type 1, AIH type 2 (n = 42), primary biliary cirrhosis (PBC) (n = 113), cryptogenic liver disease (n = 30), toxic liver disease (n = 11), primary sclerosing cholangitis (PSC) (n = 27), HCV infection (n = 25), non-alcoholic steatohepatitis (n = 43) and 100 blood donors. ASGPR Ab positivity was compared with AIH-related Abs (ANA, ASMA, Abs to LKM-1, LC-1, and SLA/LP) in patients with AIH.ResultsPatients with AIH-1 and AIH-2 demonstrated an ASGPR Ab prevalence of 29.1% and 16.7%, respectively. ASGPR Ab positivity in patients with AIH-1 and AIH-2 was not significantly different to those in patients with PSC and HCV (p > 0.05, respectively). ASGPR Ab levels in all study cohorts were significantly different with the highest medians in patients with AIH, PSC, and HCV infection (p < 0.0001). ASGPR Ab can be found as only AIH-specific Ab determined by LIA and ELISA in 24.4% of AIH patients (48/197).ConclusionsThe novel ASGPR Ab ELISA is a specific diagnostic tool for ASGPR Ab detection in AIH. In addition to AIH, patients with PSC can demonstrate elevated ASGPR Ab amongst those with ALD suggesting a tolerance break to ASGPR in PSC.