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. 2025 Jul 5:23969873251351207.
doi: 10.1177/23969873251351207. Online ahead of print.

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

Nina Jaakonmäki  1 , Tuukka Helin  2 , Timea Szanto  3 , Marialuisa Zedde  4 , Tomi Sarkanen  5 , Nicolas Martinez-Majander  6 , Juha Sinisalo  7 , Ulla Junttola  8 , Petra Redfors  9   10 , Bettina von Sarnowski  11 , Ulrike Waje-Andreassen  12 , Pauli Ylikotila  13 , Nilufer Yesilot  14 , Kristina Ryliskiene  15 , Lauri Tulkki  6 , Laura Amaya Pascasio  16 , Radim Licenik  17 , Phillip Ferdinand  18 , Eva Gerdts  19 , Dalius Jatužis  15 , Alessandro Pezzini  20   21 , Janika Kõrv  22 , Juha Huhtakangas  8 , Ana Catarina Fonseca  23 , Lotta Joutsi-Korhonen  2 , Hugoten Cate  24 , Pekka Jäkälä  1 , Jukka Putaala  6 ; SECRETO Study Group
Affiliations

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

Nina Jaakonmäki et al. Eur Stroke J. .

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.

Keywords: Antiphospholipid antibodies; ischemic stroke; young adult.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Prevalence of antiphospholipid antibodies in young ischemic stroke patients at two time-points and healthy controls at one time-point. aβ2GPI: anti-β2-glycoprotein I antibodies; aCL: anticardiolipin antibodies; LA: lupus anticoagulant. p-Values are for comparison of patients and controls, and for change in patients at baseline and 12 weeks.
See this image and copyright information in PMC

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