Antiphospholipid Antibodies Classification
The antiphospholipid antibodies are: (a) lupus anticoagulant (LA) and (c) anticardiolipin antibody (ACA). The other antibodies listed—AMA, Anti-CCP, and LKM—are autoantibodies associated with entirely different disease processes and are not classified as antiphospholipid antibodies 1.
Core Antiphospholipid Antibodies
According to the most recent 2025 ISTH guidance and the 2023 ACR/EULAR classification criteria, the three cornerstone antiphospholipid antibodies that define antiphospholipid syndrome are 1:
- Lupus anticoagulant (LA) - detected by phospholipid-dependent clotting assays
- Anticardiolipin antibodies (aCL/ACA) - IgG and/or IgM isotypes measured by ELISA
- Anti-beta2 glycoprotein I antibodies (aβ2GPI) - IgG and/or IgM isotypes measured by ELISA
These three tests remain unchanged from the revised Sapporo criteria and form the laboratory foundation for APS diagnosis 1, 2.
Why the Other Antibodies Are NOT Antiphospholipid Antibodies
AMA (Antimitochondrial Antibody)
- Associated with primary biliary cholangitis, not APS
- Targets mitochondrial antigens, not phospholipids or phospholipid-binding proteins
Anti-CCP (Anti-Cyclic Citrullinated Peptide)
- Marker for rheumatoid arthritis and predictor of erosive joint disease
- While it can occasionally be positive in SLE patients with erosive arthritis 3, it is not an antiphospholipid antibody
- Targets citrullinated proteins, not phospholipid complexes
LKM (Liver-Kidney Microsomal Antibody)
- Associated with autoimmune hepatitis type 2
- Targets cytochrome P450 enzymes in liver and kidney microsomes
- Completely unrelated to phospholipid-binding proteins
Clinical Implications
Comprehensive aPL testing requires all three tests (LA, aCL, and aβ2GPI) because triple-positive patients carry the highest risk of thrombosis and pregnancy morbidity 2. Testing must be positive on two occasions at least 12 weeks apart to meet diagnostic criteria 2.
Common Pitfall to Avoid
Do not confuse the presence of other autoantibodies in patients with systemic lupus erythematosus or other autoimmune conditions with antiphospholipid antibodies. While patients may have multiple autoantibodies simultaneously, only LA, aCL, and aβ2GPI are classified as antiphospholipid antibodies relevant to APS diagnosis and thrombotic risk assessment.