Anti-citrullinated histone H3 immunoglobulin G: new antibodies highly correlate with anti-neutrophil extracellular traps antibodies and thrombosis in antiphospholipid syndrome

Background

Neutrophil extracellular traps (NETs) are involved in the development of thrombosis. Discovering anti-NETs antibodies has provided new understanding of how NETs and thrombotic processes are connected. However, these antibodies are currently only recognized as a diverse group, with their exact makeup still unknown.

Objectives

To identify anti-citrullinated histone H3 (CitH3) immunoglobulin (Ig) G and analyze its relationship with anti-NETs antibodies and thrombosis.

Methods

We studied 38 antiphospholipid antibody-positive patients to measure anti-CitH3 IgG and anti-NETs IgG in their plasma. We examined the relationship between these antibodies and the link between anti-CitH3 IgG and thrombotic events. Additionally, we explored how anti-CitH3 IgG affects NETs clearance and platelet activation through various experiments to understand their prothrombotic mechanisms.

Results

This study demonstrated an increased incidence of thrombosis in individuals with elevated anti-CitH3 IgG levels and confirmed a robust correlation between anti-CitH3 IgG and anti-NETs IgG. Both in vitro and in vivo experiments revealed that the anti-CitH3 IgG impeded the clearance of NETs. The introduction of this antibody into a coculture of platelets and NETs resulted in elevated levels of P-selectin and CD40L, suggesting enhanced platelet activation. Furthermore, in a murine model, the presence of anti-CitH3 IgG led to increased rates of thrombosis, corroborating its role in thrombosis.

Conclusion

Anti-CitH3 IgG and anti-NETs IgG are similar and important. Anti-CitH3 IgG indirectly enhances platelet activation and exacerbates thrombosis by inhibiting NETs degradation, making it valuable for predicting thrombosis and potentially serving as a new biomarker for assessing thrombosis risk.