What antibodies are present in autoimmune hepatitis and primary biliary cholangitis (PBC)?

Antibodies in Autoimmune Hepatitis and Primary Biliary Cholangitis

The main distinguishing autoantibodies in autoimmune hepatitis (AIH) are ANA, SMA, anti-LKM1, and anti-LC1, while primary biliary cholangitis (PBC) is characterized by antimitochondrial antibodies (AMA) and specific antinuclear antibodies targeting sp100 and gp210. 1

Autoimmune Hepatitis Antibodies

Type 1 AIH (80-90% of cases)

• Antinuclear antibodies (ANA): Present in 80-96% of patients, often with SMA 1
• Smooth muscle antibodies (SMA): Present in up to 83% of patients 1
  • Most important target is F-actin 2
• Anti-soluble liver antigen/liver pancreas (anti-SLA/LP): Highly specific marker for AIH 1
  • Associated with more severe disease and higher relapse rates 1
  • Target is a 50-kd cytosolic protein (tRNP(Ser)Sec) 1
• Atypical perinuclear anti-neutrophil cytoplasmic antibodies (atypical p-ANCA): Present in 50-96% of patients 1
  • Differs from classical p-ANCA by retention of perinuclear staining on formaldehyde-fixed cells 1

Type 2 AIH (10% of cases)

• Anti-liver/kidney microsomal type 1 (anti-LKM1): The defining antibody 1
  • Target is cytochrome P450 2D6 1
• Anti-liver cytosol type 1 (anti-LC1): Often co-exists with anti-LKM1 1
• Anti-LKM3: Rarely detected 1
• p-ANCA: Typically negative (unlike Type 1 AIH) 1

Less Common/Investigational Antibodies in AIH

• Anti-asialoglycoprotein receptor (anti-ASGPR): Correlates with disease activity 1
• Anti-actin: Greater specificity for AIH than SMA 1
• Anti-Ro52/TRIM21: Often present in AIH-3 (SLA/LP positive) 1

Primary Biliary Cholangitis Antibodies

• Antimitochondrial antibodies (AMA): The hallmark antibody, present in 90-95% of patients 3
• PBC-specific antinuclear antibodies:
  • Anti-sp100: Multiple nuclear dot pattern, highly specific for PBC 4, 3
  • Anti-gp210: Perinuclear/nuclear pore pattern, highly specific for PBC 4, 3
• Anti-SS-A/Ro-52kD: Present in 28% of PBC patients, associated with more advanced disease 5
• Anti-centromere antibodies (ACA): Found in 21% of PBC patients, highly specific for PBC 5

Overlap Syndrome (PBC-AIH)

• Anti-double stranded DNA (anti-dsDNA): Associated with PBC-AIH overlap syndrome 6
• Elevated serum ALT and IgG: Significant predictors of overlap syndrome 6

Clinical Significance

1. Diagnostic value:

   • Antibody testing is crucial for initial diagnosis and classification of AIH types 1
   • Antibody titers ≥1:40 in adults support AIH diagnosis 1
   • Higher titers (≥1:80) strengthen the diagnosis 1, 2

2. Prognostic implications:

   • Anti-SLA/LP: Associated with severe disease and higher relapse rates 1
   • Anti-SS-A/Ro-52kD in PBC: Correlates with more advanced histological stage and higher bilirubin 5

3. Treatment monitoring:

   • Autoantibody titers in adults do not reliably correlate with disease activity and don't need routine monitoring 2
   • In pediatric patients, autoantibody titers may better reflect treatment response 2

Diagnostic Approach

1. Initial antibody panel for suspected AIH:

   • ANA, SMA, anti-LKM1, anti-LC1 1
   • If conventional antibodies are negative but AIH is still suspected, test for anti-SLA/LP and atypical p-ANCA 1

2. Initial antibody panel for suspected PBC:

   • AMA (primary marker)
   • Anti-sp100 and anti-gp210 (especially valuable in AMA-negative cases) 4, 3

3. For suspected overlap syndromes:

   • Complete panel including ANA, SMA, anti-SLA/LP, AMA, anti-sp100, anti-gp210 1
   • Consider anti-dsDNA testing 6

Remember that while antibodies are crucial diagnostic tools, they must be interpreted in the context of clinical presentation, liver biochemistry, histology, and exclusion of other causes of liver disease.