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29.12.2017 | Original Article

Diminished expression of β2-GPI is associated with a reduced ability to mitigate complement activation in anti-GPIIb/IIIa-mediated immune thrombocytopenia

verfasst von: Xiaolu Zhu, Jiamin Zhang, Qianming Wang, Haixia Fu, Yingjun Chang, Yuan Kong, Meng Lv, Lanping Xu, Kaiyan Liu, Xiaojun Huang, Xiaohui Zhang

Erschienen in: Annals of Hematology | Ausgabe 4/2018

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Abstract

Anti-GPIIb/IIIa-mediated complement activation has been reported to be important in the pathogenesis of immune thrombocytopenia (ITP). However, the role of the complement system and the involved regulatory mechanism remain equivocal. Beta2-glycoprotein I (β2-GPI), known as the main target for antiphospholipid autoantibodies, has been demonstrated as a complement regulator. Here, we investigated the complement-regulatory role of β2-GPI in anti-GPIIb/IIIa-mediated ITP. Plasma complement activation and enhanced complement activation capacity (CAC) were found in ITP patients with anti-GPIIb/IIIa antibodies in vivo and in vitro. Diminished plasma levels of β2-GPI were shown in patients of this group, which was inversely correlated with C5b-9 deposition. C5b-9 generation was inhibited by approximate physiological concentrations of β2-GPI, in a dose-dependent manner. Inhibition of C3a generation by β2-GPI and the existence of β2-GPI/C3 complexes in plasma indicated a regulation on the level of the C3 convertase. Furthermore, β2-GPI down-regulated the phosphorylation levels of c-Jun N-terminal kinase (JNK) and cleavage of BH3 interacting domain death agonist (Bid) and ultimately harbored platelet lysis. Our findings may provide a novel link between diminished plasma levels of β2-GPI and enhanced complement activation, indicating β2-GPI as a potential diagnostic biomarker and therapeutic target in the treatment of anti-GPIIb/IIIa-mediated ITP.

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Titel: Diminished expression of β2-GPI is associated with a reduced ability to mitigate complement activation in anti-GPIIb/IIIa-mediated immune thrombocytopenia
verfasst von: Xiaolu Zhu
Jiamin Zhang
Qianming Wang
Haixia Fu
Yingjun Chang
Yuan Kong
Meng Lv
Lanping Xu
Kaiyan Liu
Xiaojun Huang
Xiaohui Zhang
Publikationsdatum: 29.12.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 4/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-017-3215-3

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Diminished expression of β2-GPI is associated with a reduced ability to mitigate complement activation in anti-GPIIb/IIIa-mediated immune thrombocytopenia

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Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin