Which phospholipid IgM and IgG antibodies are tested besides lupus anticoagulant, β2‑glycoprotein I, and anticardiolipin?

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Last updated: October 2, 2026 • View editorial policy

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Additional Phospholipid Antibodies Beyond Standard Testing

The primary additional phospholipid antibodies tested beyond lupus anticoagulant, β2-glycoprotein I, and anticardiolipin are anti-phosphatidylserine/prothrombin (aPS/PT) antibodies, particularly IgG and IgM isotypes, though these remain non-criteria antibodies not yet recommended for routine first-line diagnostic testing. 1

Current Standard vs. Additional Testing

The 2025 ISTH-SSC guidance clearly establishes that concurrent testing should include only LA, aCL IgG/IgM, and aβ2GPI IgG/IgM as the recommended first-line panel 1, 2. However, the guidelines explicitly acknowledge additional antibodies under investigation:

Anti-Phosphatidylserine/Prothrombin (aPS/PT) Antibodies

Both IgG and IgM isotypes of aPS/PT represent the most extensively studied non-criteria phospholipid antibodies 1:

  • Prevalence in APS patients: Meta-analysis shows pooled prevalence of 50% for IgG, 45% for IgM, and 65% for either isotype 1
  • Association with thrombosis: Systematic review confirms aPS/PT as a strong risk factor for thrombosis, particularly in patients with previous thrombosis or SLE 1
  • Correlation with LA: 85% prevalence in LA-positive patients and 84% in triple-positive patients 1

Anti-Domain I β2-Glycoprotein I Antibodies (aDI)

These target specific epitopes on domain I of β2GPI and are mentioned in the 2025 guidance as requiring further research 1, 3. They may help identify pathogenic antibodies with higher specificity.

Other Investigated Antibodies (Limited Clinical Utility)

The evidence discusses but does not recommend:

  • Anti-prothrombin antibodies (without phosphatidylserine): Low diagnostic value compared to aPS/PT 1
  • Anti-annexin V antibodies: Similar prevalence in APS and SLE, not diagnostically specific 4
  • IgA isotypes of aCL and aβ2GPI: Insufficient evidence for inclusion, though association exists especially in SLE 1

Clinical Context for Additional Testing

When to Consider aPS/PT Testing

The 2025 guidance suggests aPS/PT may be useful in specific scenarios 1:

  1. Seronegative APS suspects: Patients meeting clinical criteria but negative for standard aPL panel
  2. Risk stratification: In patients with autoimmune disease to assess thrombotic risk
  3. Obstetric APS evaluation: Though added value appears limited compared to thrombotic APS 1

Important Caveats

  • Not for first-line diagnosis: The 2018 ISTH guidance explicitly states "other antiphospholipid antibody tests are not recommended yet" 2
  • Specificity concerns: 25.5% prevalence in aPL-negative patients with autoimmune disease without APS manifestations raises questions about specificity 1
  • Incomplete overlap with LA: Despite high correlation, aPS/PT cannot serve as LA surrogate since overlap is incomplete 1
  • Limited data in seronegative patients: Small studies show only 1-15% single aPS/PT positivity in suspected APS with negative standard testing 1

Practical Algorithm

For routine diagnostic workup:

  • Test LA, aCL IgG/IgM, and aβ2GPI IgG/IgM only 1, 2
  • Confirm positive results ≥12 weeks apart 1

Consider aPS/PT IgG/IgM testing when:

  • Standard aPL panel negative BUT strong clinical suspicion (thrombosis or severe pregnancy morbidity consistent with APS)
  • Risk stratification needed in SLE patients
  • Research or specialized center evaluation

Do not routinely test:

  • IgA isotypes of any phospholipid antibodies
  • Anti-prothrombin antibodies alone
  • Anti-annexin V antibodies
  • Anti-domain I antibodies (outside research settings)

The 2025 guidance emphasizes that further multicenter studies are needed to establish the role of aPS/PT in seronegative patients and to determine optimal cutoff values before these can be incorporated into routine diagnostic algorithms 1.

References

3
Research

Solid Phase Assays for Antiphospholipid Antibodies.

Seminars in thrombosis and hemostasis, 2022

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