Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review

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Abstract

To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations.

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Antibody profiles for the diagnosis of antiphospholipid syndrome

Vittorio Pengo, Alessandra Biasiolo, Cinzia Pegoraro … (2017)

Summary Among the so called‘antiphospholipid antibodies’, the presence of Lupus Anticoagulant (LA) is associated with thrombosis-related events and defines the antiphospholipid syndrome. The role of anti-cardiolipin (aCL) antibodies and anti-human β2-glycoprotein I (aβ2GPI) antibodies is less striking. Since the problem of standardization for these tests is far from resolved, we evaluated whether the combination of results (antiphospholipid laboratory profiles) could help to better classify these patients. Over a 6-year period, 618 consecutive subjects (55% of whom had previous documented thrombosis-related events) were referred to our clinic for Antiphospholipid antibody detection. LA was detected according to internationally accepted recommendations. ACL and aβ2GPI antibodies were detected by Enzyme-Linked-Immunosorbent Assay (ELISA). Patients’ records were reviewed for the presence of previous thromboembolic events or obstetric complications according to Sapporo’s clinical criteria for the diagnosis of antiphospholipid syndrome (APS) and each patient underwent a physical examination. When individual tests were considered in a multivariate analysis which took into account age, gender, the presence of SLE or other autoimmune diseases and established risk factors for venous and arterial thromboembolism, LA (Odds Ratio 4.4, Confidence Interval 1.5–13.3) and aβ2GPI antibodies (Odds Ratio 2.9, Confidence Interval 1.1–7.5) but not aCL antibodies (Odds Ratio 1.2, Confidence Interval 0.5–2.7) were found to be independent risk factors for thrombosis-related events. When antiphospholipid antibody profiles instead of individual test positivity were analyzed in the above mentioned model, triple positivity resulted a strong independent risk factor (Odds Ratio 33.3, Confidence Interval 7.0–157.6), retaining its significance when the association with venous or arterial thromboembolism was considered. Double positivity with negative LA was close to significance for thrombosis-related events (Odds Ratio 2.2, Confidence Interval1.0–5.2, p=0.056) and highly significant risk factor for obstetric complications (Odds Ratio 10.8, Confidence Interval 2.9–40.8). Other combinations did not reach statistical significance. The mean level of IgG aβ2GPI antibodies was statistically higher in triple positive profile and might account for positive LA. As compared to a single test, the analysis of a complete antiphospholipid antibody profile can better determine patients at risk.

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Functional analyses of patient-derived IgG monoclonal anticardiolipin antibodies using in vivo thrombosis and in vivo microcirculation models.

R Espinola, Xin Liu, T Olee … (2000)

Antiphospholipid antibodies (aPL) have been associated with thrombosis and pregnancy losses in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. It has been proposed that aPL may affect endothelial cell (EC) function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. It has been proposed that aPL may affect EC cell function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. This study proposes to test the hypotheses that some IgG anticardiolipins (IgG aCL) with thrombogenic properties in mice, exert their effects through activation of endothelium. We studied seven patient-derived monoclonal aCL for their thrombogenic properties in an in vivo pinch-induced thrombosis model, and their functional activities in activating EC by analyzing in vivo leukocyte adhesion to endothelium in microcirculation in venules in exposed murine cremaster muscle and in vitro adhesion molecule expression in cultured EC. The binding of the monoclonal aCL to EC was also tested. In addition to the previous identified thrombogenic IS2, four of the five new more IgG monoclonal aCL (from two patients) were found to be thrombogenic. Of these five thrombogenic aCL, three caused more in vivo leukocyte adhesion to EC in microcirculation, as compared to that induced by the H2 control human monoclonal IgG, and enhanced expression of adhesion molecules (particularly VCAM-1) on cultured EC. These data show that about 2/3 patient-derived IgG monoclonal aCL are thrombogenic and suggest that some thrombogenic IgG aCL exert their effects through activating EC.

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Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis. A multicenter study with the participation of the European Forum on antiphospholipid antibodies.

Marielle SanMarco, Jean-Robert Harlé, Marie Audrain … (2007)

A multicenter study was set up to evaluate the prevalence, clinical and biological significance of antiphosphatidylethanolamine antibodies (aPE) in thrombotic patients with or without the main known clinical and biological risk factors for thrombosis. APE and antibodies, defined as the laboratory criteria of antiphospholipid syndrome (APS) -lupus anticoagulant, anticardiolipin and anti-beta(2)-GPI antibodies were measured in 270 patients with thrombosis (234 venous and 37 arterial) and 236 matched controls. APE were found in 15% of thrombotic patients compared to 3% of controls (p < 0.001) with no predominant isotype, no association with the main known clinical or biological risk factors for thrombosis neither with a type of thrombosis, arterial or venous. In a multivariate logistic regression analysis of antibodies, aPE showed the highest association with thrombosis (odds ratio [OR]: 4.2, p < 0.001). Moreover, using a multivariate analysis in a case-control subgroup study on 158 patients, IgGaPE were found to be significantly associated with venous thrombosis (OR:6;p = 0.005). Interestingly, 25 of the 40 aPE-positive patients (63%) were negative for the APS laboratory criteria. Most of them (21/25) had venous thrombosis, recurrent in ten of them. Four patients also suffered from early or late miscarriages. Our results underline the strength of the association between the presence of aPE and thrombosis and suggest their measurement in thrombotic patients, especially when lupus anticoagulant, anticardiolipin or anti-beta(2)-GPI antibodies are absent.

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Author and article information

Journal

Title: Rheumatology

Abbreviated Title: Rheumatology

Publisher: Oxford University Press (OUP)

ISSN (Print): 1462-0324

ISSN (Electronic): 1462-0332

Publication date Created: October 13 2015

Publication date Created: November 2015

Publication date (Print): November 2015

Publication date (Electronic): July 07 2015

Volume: 54

Issue: 11

Pages: 2042-2050

Article

DOI: 10.1093/rheumatology/kev226

PubMed ID: 26152548

SO-VID: 8612dd6e-0630-4b1b-806a-61a92a112a40

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Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review

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Most cited references 6

Antibody profiles for the diagnosis of antiphospholipid syndrome

Functional analyses of patient-derived IgG monoclonal anticardiolipin antibodies using in vivo thrombosis and in vivo microcirculation models.

Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis. A multicenter study with the participation of the European Forum on antiphospholipid antibodies.

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