Contribution of anti-β2 glycoprotein1 IgA testing in the diagnosis of seronegative-APS for patients with cerebral thrombosis

Seronegative antiphospholipid syndrome has been suggested for patients with clinical manifestations highly suggestive of APS but persistently negative criteria-aPLs. Evidence gathered over the last years of research in thrombosis reported the pathogenic significance of non-criteria aPLs, among them IgA isotype. However, their role in the occurrence of neurological thrombosis, has not yet been studied. In this article, we aim to: (1) determine the prevalence of aβ2GP1 IgA in cerebral thrombosis, (2) study the association and (3) assess the diagnostic value of aβ2GP1. This study enrolled 70 patients with cerebral thrombosis without underlying autoimmune disease referred for thrombophilia assessment and 165 healthy controls. In addition to a coagulation screen and inherited thrombophilia testing, patients and controls were tested for criteria (LA; aβ2GP1; aCL IgM/IgG) and non-criteria aPLs (aβ2GP1 IgA; aCL IgA; aPS-PT; IgM/IgG). The overall aβ2GP1 IgA prevalence in patients was 61.4 % (43/70) mostly isolated in 50 % (35/70) while 50 % were positive for criteria-aPLs. aβ2GP1 IgA were the most prevalent aPLs in cerebral venous thrombosis compared with stroke (92.3 % vs 54.4 %). A significative relationship between aβ2GP1 IgA and the occurrence of CVT and stroke has been established (x² = 6.9, p = 0.008; x² = 4.03, p = 0.045). There was a high specificity of aβ2GP1 IgA testing for stroke (79 %) and CVT (100 %) despite a lower sensitivity (73 %; 52 %, respectively). The aβ2GP1 IgA testing improved considerably (50 %) the diagnosis of patients with cerebral thrombosis and negative criteria-aPLs, who may benefit from an adapted therapeutic care. Laboratory consensus criteria might consider aβ2GP1 IgA and set up a sequential approach improving APS diagnosis.