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<p>Beta-2 glycoprotein I (β2GPI) is the primary antigen targeted by thrombotic antiphospholipid antibodies and is a plasma protein with a minor inhibitory effect on blood coagulation. The results of one study suggested that β2GPI may exhibit procoagulant properties. It is important to establish the validity of this observation because β2GPI is sometimes a contaminant in therapeutic immunoglobulin (IG) products, including those associated with thrombotic complications. Unlike the previous study showing procoagulant activity in one plasma-derived lot of β2GPI, we investigated four β2GPI preparations from different vendors: three plasma-derived (pd) and one recombinant (r). No procoagulant activity was detected in two plasma-derived preparations or in the recombinant product, whereas one pd-β2GPI preparation exhibited procoagulant activity. The previous report showing procoagulant activity had also used the same vendor that showed procoagulant activity in our study. Comprehensive characterization of the pd-β2GPI associated with procoagulant activity demonstrated contamination with activated coagulation factor XI (FXIa). Furthermore, incubation of this pd-β2GPI preparation with anti-FXIa antibodies reversed the procoagulant effect. Conversely, spiking FXIa into the r-β2GPI induced a procoagulant effect. Taken together our data indicate that β2GPI exhibits no procoagulant activity, but pd-β2GPI could be contaminated with FXIa (which is a procoagulant) during the purification process. This result is consistent with a large body of work showing FXIa contamination in some lots of therapeutic IG products. These lots of IG products are associated with thrombogenicity in the clinic. Our results demonstrate that β2GPI contamination of IG lots is unlikely to be a risk factor for thrombogenicity.</p>

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The procoagulant effect described in preparations of plasma-derived β2-glycoprotein I (β2GPI) is mediated by contamination with factor XIa.

  • 期刊论文

  • 发表日期：

    2026年3月6日

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  • Yideng Liang,
  • Ivan D. Tarandovskiy,
  • Hailing Yan,
  • Yonggang Wang,
  • Stepan S. Surov,
  • Leonid A. Parunov,
  • Nancy Eller,
  • Dorothy E. Scott,
  • Zuben E. Sauna,
  • Mikhail V. Ovanesov

摘要

Beta-2 glycoprotein I (β2GPI) is the primary antigen targeted by thrombotic antiphospholipid antibodies and is a plasma protein with a minor inhibitory effect on blood coagulation. The results of one study suggested that β2GPI may exhibit procoagulant properties. It is important to establish the validity of this observation because β2GPI is sometimes a contaminant in therapeutic immunoglobulin (IG) products, including those associated with thrombotic complications. Unlike the previous study showing procoagulant activity in one plasma-derived lot of β2GPI, we investigated four β2GPI preparations from different vendors: three plasma-derived (pd) and one recombinant (r). No procoagulant activity was detected in two plasma-derived preparations or in the recombinant product, whereas one pd-β2GPI preparation exhibited procoagulant activity. The previous report showing procoagulant activity had also used the same vendor that showed procoagulant activity in our study. Comprehensive characterization of the pd-β2GPI associated with procoagulant activity demonstrated contamination with activated coagulation factor XI (FXIa). Furthermore, incubation of this pd-β2GPI preparation with anti-FXIa antibodies reversed the procoagulant effect. Conversely, spiking FXIa into the r-β2GPI induced a procoagulant effect. Taken together our data indicate that β2GPI exhibits no procoagulant activity, but pd-β2GPI could be contaminated with FXIa (which is a procoagulant) during the purification process. This result is consistent with a large body of work showing FXIa contamination in some lots of therapeutic IG products. These lots of IG products are associated with thrombogenicity in the clinic. Our results demonstrate that β2GPI contamination of IG lots is unlikely to be a risk factor for thrombogenicity.