Cited by 620Systemic Lupus Erythematosus ResearchReproductive System and PregnancyBlood Coagulation and Thrombosis Mechanisms

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Pathogenesis of antiphospholipid syndrome: understanding the antibodies

Meroni, Pier Luigi, Borghi, M. Orietta, Raschi, Elena, Tedesco, Francesco·2011·Nature Reviews Rheumatology

DOI 10.1038/nrrheum.2011.52

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Abstract

Antiphospholipid antibodies (aPL) are both diagnostic markers for, and pathogenic drivers of, antiphospholipid syndrome (APS). Although the presence of aPL is a necessary pre-condition, APS-associated clotting is seemingly triggered by an additional 'second hit', frequently related to innate inflammatory immune responses. β(2) glycoprotein I (β(2)GPI)-dependent aPL, the most important subset of these antibodies, mediate several--not necessarily alternative--thrombogenic mechanisms, mainly on the basis of their reactivity with β(2)GPI expressed on the membrane of cells that participate in the coagulation cascade. Recurrent pregnancy complications associated with aPL cannot be explained solely by thrombosis, and alternative pathogenic mechanisms have been reported. Although one in vivo model of fetal loss suggests a mechanism of aPL-mediated acute placental inflammation, other models and the histopathological examination of APS placentae do not support a widespread inflammatory signature. β(2)GPI-dependent aPL are thought to recognize their antigen on placental tissues, inhibit the growth and differentiation of trophoblasts, and eventually cause defective placentation. Why antibodies with similar antigen specificity produce different clinical manifestations is not clear. Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question.

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Authors: Meroni, P. L., Borghi, M. O., Raschi, E., & Tedesco, F.
Affiliations: University of Milan (IT)
IRCCS Istituto Auxologico Italiano (IT)
University of Trieste (IT)
Corresponding author: Meroni, Pier Luigi
ORCID: Meroni, Pier Luigi
Borghi, M. Orietta
Raschi, Elena
Tedesco, Francesco
Venue: Nature Reviews Rheumatology
Publisher: Springer Science and Business Media LLC
Published: 2011-05-10
Volume: 7
Issue: 6
Pages: 330-339
ISSN: 1759-4790 (ISSN-L)
1759-4804
DOI: 10.1038/nrrheum.2011.52
OpenAlex: W1999555834
Cited by: 620
References: 89
Citations by year: 2026: 38 · 2025: 34 · 2024: 35 · 2023: 34 · 2022: 39 · 2021: 47 · 2020: 34 · 2019: 41 · 2018: 43 · 2017: 43 · 2016: 54 · 2015: 33 · 2014: 63 · 2013: 37 · 2012: 36
FWCI: 6.72
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Rheumatology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords: antiphospholipid syndrome, antiphospholipid antibodies, beta2-glycoprotein I, thrombosis, recurrent pregnancy loss, placental inflammation, trophoblast differentiation, complement activation, innate immune response, autoantibody pathogenesis
MeSH terms: Female, Humans, Pregnancy, Pregnancy Complications, Antiphospholipid Syndrome, Antibodies, Antiphospholipid

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Pathogenesis of antiphospholipid syndrome: understanding the antibodies

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