Background: Venous thromboembolism (VTE) is still a huge challenge for Public Health. Autoimmune diseases play an increasing role in human pathologies, antiphospholipid antibody (aPL) syndrome being one of the models for VTE pathophysiology. aPL have been found to activate several signalling pathways, but we lack data on circulating antibodies-related cell activities in aPL-negative patients with VTE.

Aims: We hypothesized that certain circulating immunoglobulins G (IgG) in VTE patients might stimulate the signalling pathways involved in monocyte activation, even in aPL-negative patients (clinicaltrials.gov identifier: NCT02713581).

Methods: Plasma IgG from 13 VTE patients and 20 controls were purified by column chromatography. These purified IgG were added to a THP-1 monocyte culture medium, and proteins were extracted for subsequent western-blot analysis. Quantification of actin-normalized phospho-ERK, phospho-P38 and phospho-AKT allowed us to characterize the monocyte activation profile for each patient. Modulation of signalling pathways between groups was assessed per pathway by two-way ANOVA which also takes into account the experiment effect.

Results: Our results show a significant increase in the phospho-ERK/Actin ratio (p< 0.0001). There was no group effect concerning total protein ERK, demonstrating that activation was only due to an increase in ERK-phosphorylation (p=0.419). No significant differences were found for the other pathways (p=0.964 and p=0.174 respectively for phopsho-p38 and phospho-AKT).

Conclusions: Our pilot study shows that total IgG from patients with a history of VTE may activate the ERK pathway in the absence of antiphospholipid antibodies. The impact of this IgG-related activity on individual risks of VTE deserves to be investigated.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/activation-of-erk-signaling-pathway-by-plasma-igg-in-venous-thromboembolism-patients-without-antiphospholipid-antibodies/