Clinical Information

Clinical Background

Phospholipid (Cardiolipin) Antibodies (aCL) IgG and IgM are part of the “criteria” antiphospholipid antibody (aPL) tests used in the evaluation of antiphospholipid syndrome (APS). APS is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis and/or specific pregnancy morbidity in association with persistent aPL antibodies.

Testing may be useful in patients with:

• Unexplained arterial or venous thrombosis
• Recurrent pregnancy loss or defined pregnancy morbidity (fetal loss >10 weeks, premature birth <34 weeks due to preeclampsia/placental insufficiency, or ≥3 unexplained consecutive miscarriages <10 weeks)
• Systemic autoimmune rheumatic diseases, particularly systemic lupus erythematosus (SLE)
• Livedo reticularis or other unexplained cutaneous necrosis
• Unexplained thrombocytopenia
• Suspected nonbacterial thrombotic endocarditis

Role in APS Classification

Based on the 2006 revised Sapporo criteria and the 2023 ACR/EULAR APS classification criteria, laboratory evaluation for APS includes:

• Lupus anticoagulant (LAC)
• Anticardiolipin (aCL) IgG and IgM
• Anti–beta-2 glycoprotein I (anti-β2GPI) IgG and IgM

The 2023 ACR/EULAR criteria are primarily intended for research classification and may not always apply directly to routine clinical decision-making.

aCL IgG and IgM antibodies are detected using enzyme-linked immunosorbent assay (ELISA). These antibodies must be persistently positive on two or more occasions at least 12 weeks apart to fulfill laboratory criteria for definite APS.

Among aCL isotypes, IgG antibodies generally carry higher diagnostic relevance than IgM. Moderate-to-strong positive results (IgG or IgM ≥40 GPL/MPL units) in the appropriate clinical context are most consistent with APS.

Reference Intervals

• Negative: <15.0 MPL or GPL
• Weakly positive: 15.0-39.9 MPL or GPL
• Positive: 40.0-79.9 MPL or GPL
• Strongly positive: ≥80.0 MPL or GPL

Reference values apply to all ages.

MPL refers to IgM phospholipid units. One MPL unit is 1 microgram of IgM antibody.

GPL refers to IgG phospholipid units. One GPL unit is 1 microgram of IgG antibody.

Result Interpretation

• Results must be interpreted in conjunction with clinical findings and other laboratory tests.
• Diagnosis of APS cannot be established based on aCL results alone.
• Treatment decisions should not be based only on a positive aCL result.

aCL antibodies may be:

• Transiently elevated during infections
• Present in syphilis and other infectious conditions
• Detected at low levels in individuals without APS

Therefore, documentation of persistence is essential.

Low or isolated IgM positivity, particularly in the absence of other criteria antibodies (LAC or anti-β2GPI), has limited diagnostic specificity for APS and should be interpreted cautiously.

Inter-assay variability exists among commercial platforms. Results from different laboratories or methods may not be directly comparable due to differences in calibration, cutoff determination, and assay design.

Assay-Specific Notes

This assay is intended for the semi-quantitative detection of IgG and IgM anticardiolipin antibodies in serum. Performance characteristics have been established for serum only.

Potential limitations include:

• Rheumatoid factor (RF) interference in IgM assays
• Non-specific binding from immune complexes
• Transient positivity during infection
• Elevated results in active or seropositive syphilis

Confirmatory evaluation and clinical correlation are recommended when result