Frequency and significance of antibodies to asialoglycoprotein receptor in type 1 autoimmune hepatitis

Abstract

Antibodies to asialoglycoprotein receptor have diagnostic specificity for autoimmune hepatitis, but it is uncertain if they are complementary or redundant markers of the disease. Our aims were to assess their frequency and significance in type 1 autoimmune hepatitis and determine their contribution to the evaluation of these patients. Sera from 54 well-characterized patients were evaluated for antibodies to asialoglycoprotein receptor by a radioimmunofiltration assay based on rabbit-derived protein. Forty-four patients (82%) were seropositive. Seropositive patients were distinguished from seronegative counterparts by having higher serum gamma globulin (3.7 +/- 0.2 g/dl vs 2.3 +/- 0.3 g/dl, P = 0.0007) and immunoglobulin G levels (3707 +/- 179 mg/dl vs 2203 +/- 263 mg/dl, P = 0.0005) at presentation and a greater frequency of relapse after drug withdrawal (88% vs 33%, P = 0.01). Seropositivity for smooth muscle and/or antinuclear antibodies did not define treatment outcomes and antinuclear antibodies occurred less frequently than the other markers. Concurrent testing for antibodies to asialoglycoprotein receptor and smooth muscle identified all patients. We conclude that antibodies to asialoglycoprotein receptor are common in type 1 autoimmune hepatitis and they identify patients with a high frequency of relapse after corticosteroid withdrawal. Concurrent testing for these antibodies and smooth muscle antibodies has the same diagnostic sensitivity as testing for antinuclear and smooth muscle antibodies but a greater prognostic implication.

A novel IgM class autoantibody to a hepatocyte-related 190 kDa molecule in patients with type 1 autoimmune hepatitis

“…[1][2][3] Studies of LSP revealed that antibody to the asialoglycoprotein receptor was a specific marker of AIH. 4,5 In addition, recent evidence indicates that there may be several autoantibodies that recognize hepatocyte-associated molecules. 6 -10 We have previously reported an autoantibody to hepatocyte membrane antigen (HMA) that was detected using HepG2 cells and flow cytometry; this autoantibody was frequently found in patients with AIH but not in those with other liver diseases.…”

Autoimmune liver serology: Current diagnostic and clinical challenges

“…Anti-ASGPR antibodies are found particularly in AIH-1 (approximately 90%) but are also present in patients with PBC (14%), chronic hepatitis B and C (7%) and alcoholic hepatitis (8%) [3,52,115] . Anti-SLA antibodies can be found in occasional seronegative AIH patients i.e.…”

“…Anti-SLA antibodies are also frequently present (up to 50%, depending on the sensitivity of the method used) in typical cases of AIH-1 and AIH-2, and also in ASC [86] . Their high specificity for AiLD is has been questioned by reports of anti-SLA being present in some 10% of chronically infected HCV patients [115] . More recently, anti-SLA antibodies have been described in 22% of patients with acute liver failure (ALF) [111] .…”

“…The presence of antibodies to double stranded DNA (dsDNA) has been associated with higher levels of immunoglobulin G and higher relapse rates during immunosuppressive treatment compared to seronegative cases [119] . Seropositivity for anti-ASGPR in patients with AIH correlates with histological activity with persistence indicating unresponsiveness to immunosuppressive treatment, and re-appearance being highly suggestive of relapse especially after corticosteroid withdrawal [3,52,115,120] . Anti-SLA antibodies denote patients with a more severe course of AIH and a propensity for relapse after corticosteroid withdrawal compared to their negative counterparts [49,81,121,122] .…”

Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study

“…This treatment results in greater resolution of symptoms and of laboratory and histological abnormalities, as well as greater survival (35) . It is recommended to try to do away with medications after the achievement of clinical, biochemical and histological remission (9) . Relapse probability, however, reaches 50% in 6 months and 70% after 1 year, and sustained remission rates go down to between 10%-15% in 5 years (8,22) .…”