Resistance to annexin A5 anticoagulant activity in women with histories for obstetric antiphospholipid syndrome

Abstract

Objectives To investigate whether resistance to annexin A5 anticoagulant activity (AnxA5) occurs in women with histories for obstetric complications of antiphospholipid syndrome (Obs-APS) and whether this correlates with antibody recognition of domain 1 of β2- glycoprotein. Study Design 136 women with antiphospholipid antibodies, including 70 with histories for Obs-APS, and 30 controls, were investigated. Results Women with Obs-APS showed resistance to AnxA5 activity (median (range) 216% (130-282%) vs. controls 247% (217-283%), p<0.0001) and elevated levels of anti-domain I IgG (OD: median (range) 0.056 (0.021-0.489) vs. 0.042 (0.020-0.323); p=0.002). Those in the lowest tertile of AnxA5 anticoagulant ratios had an OR for Obs-APS APS of 58.0 (95% CI 3.3-1021.5). There was an inverse correlation between levels of annexin A5 anticoagulant activity and anti-domain I IgG. Conclusions Resistance to AnxA5 anticoagulant activity is associated with antibody recognition of domain I of β2GPI and identifies a subset of women with histories for Obs-APS.

Prevalence and Thrombotic Risk Assessment of Anti-β2 Glycoprotein I Domain I Antibodies: A Systematic Review

“…1 Two out of 11 studies, although basing their inclusion criteria on the APS diagnosis, did not specify if the APS diagnosis met the Sydney revised Sapporo guidelines. 36,41 One study out of 11 had as inclusion criteria the diagnosis of SLE that met the ACR revised criteria. 37 Two studies out of 11 had as inclusion criteria the presence of anti-β 2 GPI antibodies detected at least twice at least 12 weeks apart.…”

“…When stratifying patients for inclusion criteria used to enroll subjects in each study, a frequency of anti-β 2 GPI-DI positivity of 38.6% was found in those studies enrolling patients with APS according to the Sapporo criteria, 35,[38][39][40]43,44 25.1% in studies including patients with SLE (according to ACR revised criteria), 37 40.3% in patients with APS (without any details about Sydney or Sapporo criteria), 36,41 and 57.9% in those studies that aimed to assess the frequency of anti-β 2 GPI-DI positivity in presently antiβ 2 GPI positive patients. 9,42 As would be expected, and due to selection bias, an overall statistically significant higher antiβ 2 GPI-DI positivity was seen in the two studies that used as inclusion criteria the presence of anti-β 2 GPI positivity detected at least twice at least 12 weeks apart 9,42 when compared with the other studies (►Table 5).…”

Insights into the pathophysiology of the antiphospholipid syndrome provided by atomic force microscopy

“…In accordance with this idea, our own clinical studies have indicated that while a substantial proportion of patients with APS have evidence for antibodies that disrupt AnxA5 anticoagulant activity, a subset of patients do not show evidence for this disruption (Rand et al, 2004; Hunt et al, 2011), suggesting that other aPL-mediated disease mechanisms may also be operative in individual patients.…”

The Significance of Antibodies against Domain I of Beta-2 Glycoprotein I in Antiphospholipid Syndrome

“…In vitro, antidomain I antibodies were found to display LA activity. 16,25 Furthermore, antidomain I antibodies have been shown to increase resistance against the anticoagulant properties of annexin A5 and against activated protein C. [25][26][27][28][29] LApositive anti-β 2 GPI antibodies, isolated from a subset of patients with APS, were found to neutralize the inhibitory function of β 2 GPI on von Willebrand factor induced platelet aggregation. 30 Given the fact that antidomain I antibodies display LA activity, this effect may be mediated by antidomain I antibodies.…”