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

the SECRETO Study Group, Nina Jaakonmäki, Tuukka Helin, Timea Szanto, Marialuisa Zedde, Tomi Sarkanen, Nicolas Martinez-Majander, Juha Sinisalo, Ulla Junttola, Petra Redfors, Bettina von Sarnowski, Ulrike Waje-Andreassen, Pauli Ylikotila, Nilufer Yesilot, Kristina Ryliskiene, Lauri Tulkki, Laura Amaya Pascasio, Radim Licenik, Phillip Ferdinand, Eva GerdtsDalius Jatužis, Alessandro Pezzini, Janika Kõrv, Juha Huhtakangas, Ana Catarina Fonseca, Lotta Joutsi-Korhonen, Hugoten Cate, Pekka Jäkälä, Jukka Putaala

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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.

Original languageEnglish
Article number23969873251351207
JournalEuropean Stroke Journal
DOIs
Publication statusE-pub ahead of print - 5 Jul 2025
Publication typeA1 Journal article-refereed

Keywords

  • Antiphospholipid antibodies
  • ischemic stroke
  • young adult

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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