Anti-beta2-glycoprotein I IgG antibodies are associated with early-onset cryptogenic ischemic stroke

Abstract Background Previously undetected antiphospholipid antibodies (aPLs) potentially provide explanations for early-onset cryptogenic ischemic stroke (CIS). Prior association studies conducted over a decade ago were inconclusive and not focused on patients with CIS. Methods SECRETO is a multi-center case-control study enrolling patients aged 18–49 years with imaging-positive acute CIS and 1:1 matched stroke-free controls. Lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2-glycoprotein I (aβ2GPI) IgG antibodies were assessed from blood samples taken at two time points (baseline and 12-weeks) from patients and at a single time point from controls. Conditional logistic regression models assessed the association of aPLs, adjusted for age, level of education, and vascular risk factors. Results A total of 503 patient-control pairs were analyzed. At either time-point, compared to healthy controls, patients had more frequently positive aβ2GPI (patients 11.9% vs controls 2.0%, p 0.001). There was no significant difference in the presence of positive LA between patients and controls. In the logistic regression model, at either time-point positive aB2GI and aCL were associated with CIS (odds ratio OR 11.22, 95% confidence interval CI 4.35–28.95 and OR 20.85, 95% CI 204–213.16, respectively). The frequency of patients with positive aβ2GPI or aCL increased from baseline to 12 weeks (p 0.001), whereas frequency of positive LA results decreased (p 0.001). Conclusions Positive aβ2GPI and aCL, but not LA, detected either shortly after stroke or after 12 weeks were associated with early-onset CIS. Notably, after the acute phase, frequencies of positive aβ2GPI and aCL increased, whereas LA showed a reverse trend.