Antiphospholipid antibody trajectories and clinical correlates in an inception cohort of systemic lupus erythematosus

Objective

To evaluate longitudinal antiphospholipid antibody (aPL) patterns in newly diagnosed systemic lupus erythematosus (SLE) and their association with vascular events, disease activity and organ damage.

Methods

We conducted a prospective study within the INSPIRE registry including patients with newly diagnosed SLE (median disease duration 232 days [114-484]) with serum at baseline, 6 and 24 months. Anti-cardiolipin (aCL) and anti-beta2 glycoprotein I (anti-β2GPI) IgG/IgM were measured by ELISA; lupus anticoagulant when feasible. aPL positivity was analysed using manufacturer cut-offs and moderate–high titres (>40 U). Patients were classified as persistently negative, positive, fluctuating or negativised. High- and low-risk aPL profiles were defined per EULAR recommendations. Associations with thrombosis, SLEDAI-2K, Physician Global Assessment (PGA) and SLICC/ACR Damage Index (SDI) were assessed.

Results

Among 270 patients, 77.1% were aPL-positive at least once, predominantly low-titre. Moderate–high titre aPLs were less frequent and stable. Most patients with baseline negativity or low-titre/single positivity reverted to negative, whereas dual or triple positivity was associated with persistence. A subgroup (3.1%) progressed from negative/low-titre to high-risk profiles. aPL negativisation occurred in 12.5% and was inversely associated with baseline aPL burden. Over two years, 19 (7%) developed thrombosis, with higher risk in high-risk and persistently positive groups; no thrombotic events occurred in persistently aPL-negative patients.

aPL titres did not correlate with SLEDAI-2K or PGA, while aCL IgG and anti-β2GPI IgG correlated weakly with anti-dsDNA. SDI remained low across groups.

Conclusion

In early SLE, aPLs are largely low-titre and fluctuating, with some patients evolving to higher-risk states, supporting serial aPL testing