Annexin A5 polymorphism (−1C→T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome

Abstract

Background: Annexin A5 is thought to have a role in the pathophysiology of the antiphospholipid syndrome (APS)-a syndrome characterised by recurrent thrombosis and pregnancy morbidity. Objective: To investigate whether anti-annexin A5 immunoglobulin (Ig)M or IgG antibodies, or the 21CRT polymorphism of annexin A5, is a risk factor for thrombosis or miscarriage, and whether the 21CRT polymorphism is correlated with APS. Methods: A cohort study was carried out with a population of 198 patients with primary APS, systemic lupus erythematosus or lupus-like disease. For the detection of anti-annexin A5 antibodies and the measurement of annexin A5 plasma levels, ELISA-type methods were used. The annexin A5 21CRT mutation was detected by restriction fragment length polymorphism. Results: 71 patients were positive for annexin A5 IgM or IgG antibodies, of whom 53 patients were positive for anti-annexin A5 IgG antibodies and 27 of 198 patients were positive for anti-annexin A5 IgM antibodies. The prevalence of IgM or IgG anti-annexin A5 antibodies was not significantly associated with thrombosis or miscarriage on multivariate analysis. The prevalence of the 21CRT mutation in the annexin A5 gene (46/198 patients) was significantly associated with miscarriage (odds ratio 2.7, 95% confidence interval 1.1 to 6.7, independent risk factor). Conclusion: The detection of anti-annexin A5 antibodies does not seem relevant for estimating the risk for thrombosis or miscarriage in APS. The 21CRT mutation was an independent risk factor for miscarriage, which is independent of APS.

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2)

“…Actually, other studies reported an association of antiannexin antibodies with peculiar autoimmune conditions, such as discoid lupus 25 and antiphospholipid syndrome, typically a serious condition potentially causing vascular events. [26][27][28] Therefore, our results go in the direction of other reports that already suggested a generic implication of antihistones, anti-DNA, and antipodocyte antibodies. 11,29,30 Looking at the renal composition of autoantibodies, a relevant finding here is the preponderance in glomeruli of antibodies of the IgG2 isotype (anti-a-enolase/annexin AI and H3 histone) with little amounts of anti-DNA IgG3 and predominant colocalization of anti-IgG4 with C1q in subepithelial deposits of class V biopsies.…”

Diagnostic significance of anti-annexin-A5 antibody determination

“…Other investigators have not found enough data to support the diagnostic role of these antibodies [22][23][24][25]33,39]. The discrepancies among these studies are mainly due to the different diagnostic criteria used, the different disease stages and the different methods of determination of a-A5 [41].…”

“…Moreover, in this study the only significant risk factor for fetal loss in these patients were a-A5. On the other hand, de Laat et al [33] share the contrary opinion that a-A5 are not a risk factor for thrombosis or a pregnancy loss in patients with APS and SLE but the mutations in the A5 gene are an independent risk factor for thromboses and fetal loss, apart from the APS.…”

Genotyping analysis for the 46C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss

“…Many cross-sectional studies have been reported on associations between polymorphism and RPL, such as 4G/4G for plasminogen activator inhibitor-1 polymorphisms (OR 11.0, 95% CI 2.3-52.4), protein Z intron F G79A polymorphism (OR 0.3, 95% CI 0.1-0.8) and Annexin A5's -1C/T (OR 2.7, 95% CI 1.0-6.7) [27][28][29]. However, the clinical significance could not be established because most were not cohort studies.…”