Is cardiolipin antibody different from anti-phospholipid (Anti-Phospholipid) antibody?

Anticardiolipin Antibody vs. Antiphospholipid Antibody: Understanding the Relationship

Anticardiolipin antibody (aCL) is a specific type of antiphospholipid antibody (aPL), not a separate entity. Anticardiolipin antibodies are one of the three main laboratory criteria used to diagnose antiphospholipid syndrome (APS), alongside lupus anticoagulant (LA) and anti-β2-glycoprotein I (aβ2GPI) antibodies 1.

Relationship Between aCL and aPL

Antiphospholipid antibodies (aPL) represent a heterogeneous group of autoantibodies directed against phospholipids and phospholipid-binding proteins. The three main types include:

1. Anticardiolipin antibodies (aCL):

   • Target cardiolipin (a specific phospholipid) in the presence of β2-glycoprotein I
   • Detected using solid phase immunoassays (ELISA or automated systems)
   • Include IgG and IgM isotypes
   • Less specific but more prevalent than lupus anticoagulant 1

2. Anti-β2-glycoprotein I antibodies (aβ2GPI):

   • Target β2-glycoprotein I directly
   • More specific for APS diagnosis
   • Include IgG and IgM isotypes 1

3. Lupus anticoagulant (LA):

   • Detected using phospholipid-dependent coagulation tests
   • More specific but less prevalent than anticardiolipin antibodies
   • Strongest association with thrombotic risk 1

Important Clinical Distinctions

• Specificity differences: aCL immunoassays detect a broader array of autoantibodies, including both cofactor-dependent and cofactor-independent antibodies, while aβ2GPI assays are more specific for β2GPI-dependent antibodies 1.

• Clinical significance:

  • Triple positivity (LA, aCL, and aβ2GPI) carries the highest risk for thrombosis and pregnancy morbidity 1, 2
  • Isolated aCL positivity has variable clinical significance and may reflect antibodies directed against cardiolipin itself or to cardiolipin-binding proteins different from β2GPI 1
  • IgG isotypes generally have higher odds ratios for clinical events than IgM isotypes 3

• Testing recommendations: The International Society on Thrombosis and Haemostasis (ISTH) recommends testing for all three antibodies concurrently to properly assess the risk profile 1, 2.

Diagnostic Implications

For proper diagnosis of APS, the American College of Rheumatology and ISTH recommend:

• Testing for all three antibodies (LA, aCL, and aβ2GPI)
• Including both IgG and IgM isotypes for aCL and aβ2GPI
• Confirming positive results on two occasions at least 12 weeks apart
• Using a cutoff of >99th percentile or >40 units for moderate-high positivity 1, 2

Clinical Relevance

Understanding the relationship between these antibodies is crucial for:

• Accurate diagnosis of APS
• Risk stratification for thrombotic events and pregnancy complications
• Guiding appropriate treatment decisions
• Interpreting laboratory results correctly

Potential Pitfalls

• Isolated aCL testing without the complete panel may miss clinically significant APS
• Transient aPL positivity can occur with infections and certain medications
• Laboratory methods and cutoff values vary between testing facilities
• Testing during anticoagulant therapy may affect results, particularly for LA 1, 2

In summary, anticardiolipin antibody is a specific type of antiphospholipid antibody that targets cardiolipin in the presence of β2-glycoprotein I. Comprehensive testing for all three main types of antiphospholipid antibodies provides the most accurate assessment of clinical risk.