Persistence of Anti-cardiolipin and Anti-β2 Glycoprotein-1 Antibodies across Isotypes and Titers

BACKGROUND: The 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology antiphospholipid syndrome classification criteria gave higher scores to IgG than IgM anti-β2 glycoprotein-1 (aB2GP1) and anticardiolipin (aCL) antibodies. The objective of this study is to correlate aB2GP1/aCL antibody titers and isotypes with persistence. METHODS: Results from 6863 and 4755 unique patients who underwent repeat testing (>80 days) for aB2GP1-IgG/IgM and aCL-IgG/IgM antibodies, respectively, were categorized into 4 groups based on titer: negative (<10), weak-positive (10-39), moderate-positive (40-79), and high-positive (≥80). The percentage of persistence of each antibody across the 4 titer groups was calculated. RESULTS: At repeat testing, >95% of negative aB2GP1-IgM/IgG and aCL-IgG results remained negative. However, 16.2% of negative aCL-IgM patients became weak-positive. Weak-positive titers are more likely to change to moderate/high-positive (2.6%-7.8%) than negative (0.1%-0.7%). Among weak-positive patients, aCL-IgM persisted longer and was less likely to become negative (21.1%) than aCL-IgG (47.6%). In the high-positive range, 91.3% of aB2GP1-IgG, 92% of aCL-IgG, and 87.5% of aB2GP1-IgM patients remained moderate/high-positive. aCL-IgM was the least persistent, with 19.4% decreasing to weak-positive/negative on repeat testing. In a 7-year period, only the mean titers of aCL-IgM were transiently elevated, possibly due to population-wide COVID-19 infections and/or vaccinations. CONCLUSIONS: Higher titers correlate with persistence. aB2GP1-IgM/IgG and aCL-IgG antibodies show no notable differences in persistence. aCL-IgM is more prone to titer changes, and in the weak-positive range, it may indicate non-antiphospholipid syndrome-specific responses.