Autoantibodies In Autoimmune Hepatitis Research Articles

Review article: unanswered clinical and research questions in autoimmune hepatitis-conclusions of the International Autoimmune Hepatitis Group Research Workshop.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that results in substantial morbidity and mortality with many unanswered clinical and research questions. Improved understanding of disease pathogenesis, including the extra-hepatic manifestations of AIH, may allow targeted treatments with greater efficacy and fewer associated adverse events. To identify the spectrum of unanswered clinical and research questions facing care providers in the management of patients with autoimmune hepatitis (AIH). The International Autoimmune Hepatitis Group initiated a series of research workshops to start to address these questions. Key issues were discussed in small group sessions with collation of all discussions to be summarised in this manuscript. Key issues were identified as: the need for better understanding of disease pathogenesis, standardisation of the methods and assays used to evaluate autoantibodies in AIH, refinement of the histopathological criteria for "typical" or "compatible" AIH, focus on the interaction with non-alcohol related fatty liver disease, how to treat acute severe AIH, better assessment of quality of life in adults and paediatrics, standardising use of standard, third-line and experimental therapies in AIH and search for biomarkers early in the disease course that predict outcome. This workshop has outlined the key unanswered clinical and research questions to help to define the research agenda in AIH.

The importance of autoantibody detection in autoimmune hepatitis.

The autoantibodies in autoimmune hepatitis (AIH) are extensively used for its diagnosis and classification. However, they are also useful for defining the prognosis and inferring clinical behavior.

Detection of D‐3‐phosphoglycerate dehydrogenase autoantibodies in patients with autoimmune hepatitis: Clinical significance evaluation

D-3-phosphoglycerate dehydrogenase (3-PHGDH) was identified as a putative target of autoantibodies in autoimmune hepatitis (AIH). The aims of the present study were to detect anti-3-PHGDH in patients with AIH and other chronic liver diseases and to analyze their clinical relevance. Human 3-PHGDH gene was cloned and expressed in Escherichia coli and used in enzyme-linked immunosorbent assays and Western blots. Serum from patients with AIH (n = 101), primary biliary cirrhosis (PBC, n = 122), chronic hepatitis C (CHC, n = 117), chronic hepatitis B (CHB, n = 112), and from patients with other autoimmune disease (n = 125) were investigated. The highest incidence and activity of anti-PHGDH was observed in AIH patients. Thirty-two of 40 untreated (80%) and 37 of 61 AIH patients treated with corticosteroid (60.7%) were positive. Antibody titers decreased significantly during corticosteroid treatment. 15.8% of PBC patients, 9.8% of CHB and 12.8% of CHC patients, were anti-PHGDH-positive, with less than 12% of patients positive with other autoimmune diseases via reactions with recombinant 3-PHGDH protein. Anti-PHGDH were detected in chronic liver diseases. They occur predominantly in AIH, and corticosteroid treatment seems to decrease antibody titers. Whether the antibodies are primary or secondary phenomena and whether they are related to the etiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.

Serologic Markers for Autoimmune Hepatitis

Antinuclear antibodies (ANAs) and antismooth muscle antibodies (ASMAs) are the most common serologic markers for the presence of autoimmune hepatitis (AIH), but up to 30% of patients with AIH do not show elevated titers. To investigate whether the presence of autoantibodies in AIH correlates with clinical presentation, …

Serum proteomic-based analysis for the identification of a potential serological marker for autoimmune hepatitis

In the present study, by using a serologic proteomic analysis, we identified phosphoglycerate mutase isozyme B (PGAM-B) as a putative target of autoantibodies in autoimmune hepatitis (AIH). To evaluate whether the identified autoantigen is crucial for AIH, we cloned PGAM-B cDNA and expressed the recombinant protein in Escherichia coli. The soluble PGAM-B was purified by affinity chromatography and used as a coating antigen to determine the frequency of the PGAM-B-autoantibodies (PGAM-B-Abs) in patients with AIH and primary biliary cirrhosis (PBC) as well as chronic hepatitis B (CHB), chronic hepatitis C (CHC), and healthy donors by ELISA. Our study showed that the autoantibody to PGAM-B was predominantly present in AIH patients and 70.04% (50/71) of the tested AIH sera reacted to PGAM-B. The frequency of autoantibodies to PGAM-B is much higher in patients with AIH than in patients with PBC, CHB, CHC, and normal control. The data were further confirmed by using 1-DE Western blot analysis. Our study presents the first description of this protein as a candidate of diagnostic marker for AIH.

553 Prevalence of RO/SSA autoantibodies in autoimmune hepatitis and association with unexplained pregnancy loss

553 Prevalence of RO/SSA autoantibodies in autoimmune hepatitis and association with unexplained pregnancy loss

Prevalence of Autoantibodies to the p53 Protein in Autoimmune Hepatitis

The target antigens of anti-nuclear autoantibodies in autoimmune hepatitis (AIH) are poorly characterised. Since antibodies to the p53 nuclear protein have been reported in various autoimmune diseases, we have assessed the prevalence of these antibodies in patients with AIH (n = 45), primary biliary cirrhosis (n = 60), hepatitis B (n = 22), hepatitis C (n = 55), and in a control group of subjects with various non-liver diseases (n = 56). A significant proportion of patients with AIH (31%) had elevated levels of autoantibodies to the p53 protein. In contrast, the prevalence of these antibodies in primary biliary cirrhosis (8%) and viral hepatitis (6%) was similar to that in the control group (4%). The clinical features of the anti-p53 seropositive AIH patients were similar to those of the seronegative ones. Thus, the prevalence of p53 autoantibodies in AIH is higher than in other forms of chronic hepatitis, and may be useful in differential diagnosis.

LKM autoantibodies in autoimmune hepatitis, APS1 and chronic hepatitis C: quantification of anti-CYP2D6 autoantibodies with 35S-labeled recombinant protein and comparison of target proteins

LKM autoantibodies in autoimmune hepatitis, APS1 and chronic hepatitis C: quantification of anti-CYP2D6 autoantibodies with 35S-labeled recombinant protein and comparison of target proteins