Diagnostic autoantibodies for autoimmune liver diseases

Abstract

Autoimmune liver diseases are conditions of low prevalence that comprise the triad of autoimmune hepatitis, primary biliary cholangitis (cirrhosis) and primary sclerosing cholangitis and their poorly characterised overlapping syndromes. Diagnostic autoantibodies are associated with autoimmune hepatitis and primary biliary cholangitis but not with primary sclerosing cholangitis. Autoantibodies are useful disease markers that facilitate early diagnosis of autoimmune hepatitis and primary biliary cholangitis and allow for therapeutic intervention to prevent progression to liver cirrhosis and associated complications. Adult onset type 1 autoimmune hepatitis is associated with F-actin reactive smooth muscle autoantibody, antinuclear autoantibody in 60% of patients, and autoantibody to SLA/LP in 15–20%. Juvenile onset type 2 autoimmune hepatitis is associated with LKM-1 and LC-1 autoantibodies. Primary biliary cholangitis is associated with a mitochondria-associated autoantibody designated M2 in >90% of patients and with disease-specific antinuclear autoantibodies in 50% that bind to antigens in the nuclear core complex and in multiple nuclear dots. Autoantibodies to the nuclear core complex target gp210, nucleoporin p62 and nuclear lamin B receptor. Autoantibodies to multiple nuclear dots target Sp100 and PML antigens. Liver autoantibodies in asymptomatic patients with normal liver function may precede the subsequent development of overt autoimmune liver disease. For routine diagnostic immunology laboratories, initial screening for liver autoantibodies by immunofluorescence remains the method of choice with confirmation for reactivity with their target antigen by enzyme-linked immunosorbent assay (ELISA) or line blot when required.

Serological Differential Diagnosis of Autoimmune Liver Diseases by Line Blot Immunoassay for Parallel Detection of Nine Different Autoantibodies

“…Autoimmune liver diseases, although their low prevalence, lead to liver cirrhosis progression and death from liver failure. They represent the triad of autoimmune hepatitis (AIH), primary biliary cholangitis (cirrhosis) (PBC), and primary sclerosing cholangitis (PSC), along with overlapping syndromes [1]. Liver autoantibodies have a validated role in early diagnosis of these patients, particularly in asymptomatic ones, before the development of clinical symptoms [1].…”

“…They represent the triad of autoimmune hepatitis (AIH), primary biliary cholangitis (cirrhosis) (PBC), and primary sclerosing cholangitis (PSC), along with overlapping syndromes [1]. Liver autoantibodies have a validated role in early diagnosis of these patients, particularly in asymptomatic ones, before the development of clinical symptoms [1]. Moreover, early identification of the disease and subsequent early therapeutic intervention by immunosuppression for AIH and by ursodeoxycholic acid (UDCA) for PBC can control disease progression [2].…”

“…By autoantibody profile and by age of onset, AIH can be divided into type 1 and type 2. However, both types could not be distinguished by their clinical presentation alone [1,4]. Asymptomatic patients at the time of diagnosis may have a good prognosis without administration of immunosuppressive therapy [1].…”

“…PBC is a progressive liver disease characterized by destruction of small intrahepatic bile ducts leading to cholestasis and eventually cirrhosis. Early diagnosis is also crucial as the disease can be controlled by UDCA [1], as mentioned above. The diagnostic criteria include definite liver histopathology of granulomas around the bile ducts, the presence of liver autoantibodies to mitochondria, as well as PBC-specific anti-nuclear autoantibodies (ANA), along with elevated serum alkaline phosphatase [5].…”

The immune system of the liver: 50 years of strangeness

“…The final three reviews of this special issue are more clinically orientated. Ban‐Hok Toh 12 provides an overview of the diagnostic antibodies that differentiate the various subtypes of auto‐immune liver disease, emphasising that further definition and stratification of these pathologies—as well as better understanding of the underlying immune processes—is needed to bring forward better therapies for this complex group of severe chronic diseases.…”