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Clinical value of amyloid-beta1-40 as a marker of thromboinflammation in Antiphospholipid Syndrome

Lookup NU author(s): Dr Nikolaos VlachogiannisORCiD, Professor Konstantinos StellosORCiD, Professor Kimon Stamatelopoulos



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Oxford University Press, 2021.

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Abstract. OBJECTIVE: Amyloid-beta1-40 (Aβ40) is a pro-inflammatory peptide under investigation as a novel biomarker of vascular inflammation, endothelial dysfunction and atherothrombosis in the general population. Herein, we tested the hypothesis that Aβ40 is deregulated in antiphospholipidsyndrome (APS), a systemic autoimmune disease characterized by thrombo-inflammatory state. METHODS: Between January 2016 and July 2017, we consecutively recruited 80 regularly followed thrombotic APS patients (44 primary, 36 systemic lupus erythematosus/APS) and 80 age and sex-matched controls. Plasma Aβ40 levels were measured using ELISA and APS-related clinical and laboratory characteristics were recorded. The adjusted Global Anti-Phospholipid Syndrome Score (aGAPSS), a validated risk score in APS, was calculated as a comparator to Aβ40performance to detect arterial thrombotic APS-related events. RESULTS: Higher Aβ40 levels were significantly associated with the presence of APS (OR:1.024per 1 pg/ml, 95%CI 1.007-1.041) after adjustment for cardiovascular risk factors (CVRFs)including smoking, arterial hypertension, dyslipidemia, body mass index, and for estimated glomerular filtration rate (eGFR). Among APS patients, increased hsCRP serum levels was the only independent determinant of Aβ40 levels. Importantly, Aβ40 levels above the optimal ROC derived cutoff value were independently associated with recurrent arterial events (OR:4.93, 95%CI1.31-18.51) after adjustment for age, sex, CVRFs, hsCRP, and high anti-β2GPI IgG titers. Finally, by ROC curve analysis, Aβ40 provided incremental additive value over aGAPSS by significantly improving its discrimination ability for recurrent arterial thromboses. CONCLUSION: In APS, Aβ40 plasma levels are elevated and associated with an adverse thrombo-inflammatory profile. The pathophysiological and prognostic role of Aβ40 in APS merits further investigation.

Publication metadata

Author(s): Tektonidou MG, Kravvariti E, Vlachogiannis NI, Georgiopoulos G, Mantzou A, Sfikakis PP, Stellos K, Stamatelopoulos K

Publication type: Article

Publication status: Published

Journal: Rheumatology

Year: 2021

Volume: 60

Issue: 4

Pages: 1669-1675

Print publication date: 01/04/2021

Online publication date: 07/10/2020

Acceptance date: 28/07/2020

Date deposited: 30/07/2020

ISSN (print): 1462-0324

ISSN (electronic): 1462-0332

Publisher: Oxford University Press


DOI: 10.1093/rheumatology/keaa548


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