Autoantibodies as Prognostic Markers in Autoimmune Liver Disease

Abstract

Certain autoantibodies in autoimmune liver disease have prognostic implications that are under-utilized and under-developed. The goals of this review are to indicate progress in characterizing the autoantibodies with prognostic connotations and to indicate the feasibility and importance of discovering other markers. Prime source and review articles in English were selected by a Medline search through 2010. Antibodies to soluble liver antigen, actin, liver cytosol type 1, asialoglycoprotein receptor, chromatin, cyclic citrullinated peptide, and uridine glucuronosyltransferases have been associated with the occurrence, severity, and progression of autoimmune hepatitis, and antibodies to Sp100, gp210, and centromere have had similar implications in primary biliary cirrhosis. Antibodies to soluble liver antigen have shown the most promise in autoimmune hepatitis as they have been associated with severe histological changes, long durations of treatment, relapse after drug withdrawal, and high frequency of liver failure. Antibodies to the nuclear rim pore protein, gp210, have shown the most promise in primary biliary cirrhosis as they have been associated with severe interface hepatitis, lobular inflammation, and progression to liver failure. The major limitations of the autoantibodies have been their lack of standardized assays, low negative predictabilities, and fluctuating levels. Performance parameters will improve as critical pathogenic pathways, comprehensive testing batteries, and standardized assays through international exchange workshops are developed. Progress has been made in identifying the serological markers of prognosis in autoimmune liver disease, and they promise to reflect critical disease mechanisms and enhance patient management.

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

“…A similar mechanism may be in effect in Traf6ΔTEC mice, as antigen presentation was indeed compromised by mTEC depletion in these animals. In addition, our observation of anti-SLA autoantibodies present in the sera of Traf6ΔTEC mice supports faulty antigen presentation in these mice, as anti-SLA autoantibody production has been linked to HLA DRB1*0301 alleles (33,58), which, together with DRB1*0401 alleles, are the principal genetic risk factors for development of type 1 AIH in certain patients (30,(34)(35)(36).…”

“…In addition, anti-soluble liver antigen (anti-SLA) antibodies serve as highly specific serological markers for AIH and exhibit 99% specificity for diagnosing this disease (30)(31)(32)(33). Anti-SLA antibodies have been found in 11%-22% of white North American and northern European adult patients with type 1 AIH and are common (18%-44% incidence) in children with type 1 and type 2 AIH (30,(34)(35)(36). To further characterize the nature of the autoantibodies in Traf6ΔTEC mice, we tested for the presence of anti-SLA, anti-SMA, and anti-LKM autoantibodies.…”

Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease

“…Hence, it was proposed as an injury-specific marker [28]. There is evidence that the presence of anti-F-actin-Abs may worsen the prognosis in autoimmune hepatitis [29]. We observed that in patients with advanced liver failure (CTP class B and C) anti-F-actin-Abs were more frequently detected and were associated with a higher concentration of serum IL-22.…”

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

“…Its presence identifies patients with a more severe disease and a worse outcome. It is also associated with HLA-DR3 (28,29) .Anti-LC1 is the second marker of AIH-2, detected in 24% to 32% of patients with anti-LKM1 and rarely as the only marker of AIH-2. It occurs mainly in young patients with an aggressive disease course with rapid progression to cirrhosis (30,31) .…”

“…It occurs mainly in young patients with an aggressive disease course with rapid progression to cirrhosis (30,31) . The perinuclear anti-neutrophil cytoplasm (pANCA) antibody and anti-asialoglycoprotein receptor antibody (ASGPR) are less frequently used in clinical practice since they are not specific for the diagnosis of AIH (29,32) . To better standardize the diagnosis of AIH, the International AIH Study Group (IAIHSG) have stablished a scoring system in 1993 to define AIH as probable or definite (12) .…”