Heterogeneity of antiphospholipid antibody profiles in a clinical cohort and association with distinct clinical features.

BACKGROUND

The diagnosis of antiphospholipid syndrome (APS) uses standard antibodies (lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, β2-glycoprotein I antibodies (β2GPI) IgG/IgM), which results in some patients with 'seronegative APS' being overlooked. The diagnostic value of an extended antibody profile, including antiphosphatidylserine/prothrombin complex (aPS/PT) and aCL/β2GPI IgA, requires clarification.

OBJECTIVE

This study aimed to define antibody heterogeneity in APS and determine the diagnostic and risk-stratification value of novel antibodies.

METHODS

We retrospectively enrolled 2994 patients with clinical features suggestive of APS who underwent testing for criteria antibodies (LAC, aCL IgG/IgM and β2GPI IgG/IgM) and extended markers (aPS/PT IgG/IgM and aCL/β2GPI IgA). Principal component analysis (PCA) explored antibody reactivity patterns. Multivariate logistic regression identified independent diagnostic predictors, and receiver operating characteristic curve analysis evaluated diagnostic performance. Associations between antibodies and clinical parameters defined clinical phenotypes.

RESULTS

PCA revealed three dimensions explaining 73.56% of variance: principal component (PC)1 (IgG/LAC axis; 41.42%), PC2 (specific IgM axis; 18.12%) and PC3 (specific IgA axis; 14.02%). aPS/PT-IgM was a strong independent predictor of clinical diagnosis (adjusted OR 1.147, 95% CI 1.129 to 1.165, p<0.001). The area under the curve for diagnosing triple-negative APS was 0.868 for aPS/PT-IgM. Standard criteria antibodies lost independent significance in the full model. Phenotypic analysis identified three subtypes: a 'classical type' (PC1-High) with prolonged coagulation times and complement consumption; an 'inflammatory type' (PC3-High) with elevated systemic inflammation markers without complement consumption; and a 'restricted type' (PC2-High) associated with anaemia.

CONCLUSION

Distinct antiphospholipid antibody heterogeneity exists, categorisable into 'classical', 'inflammatory' and 'restricted' subtypes. This study identifies aPS/PT-IgM as a strong independent serological marker associated with clinical status. Incorporating aPS/PT-IgM into routine testing could significantly reduce seronegative APS misdiagnosis.