FXII Specific Neutra™ Antibody Products

FXII (Coagulation factor XII), also named as Hageman factor (HAF), is an 80-kDa plasma protein primarily synthesized in the liver, which is recognized as the plasma zymogen precursor of the serine protease factor XIIa (FXIIa). When blood is exposed to biological or artificial surfaces or when pathologic surfaces arise in disease states, FXII switches to FXIIa by plasma kallikrein (PKa) or by binding to negatively charged surfaces to auto-activate itself, thus initiating a series of proteolytic cascades and modulating multiple endothelial cell functions. Monoclonal antibodies against FXII have been generated and hold potential as useful tools for research applications.

Fig. 1 A model for two-stage activation of Factor XII. ^{1, 3}

Its Gene ID: 2161, UniProtKB ID: P00748, and OMIM ID: 610619.

Roles of FXII in Diseases

• FXII Deficiency

As FXII plays a critical role in the activation of the intrinsic coagulation system, FXII deficiency is a rare harbinger of complications, inherited in an autosomal recessive manner. This disorder brings the patients higher risks of acquired thrombotic disorders and developing deep venous thrombosis. The symptoms of FXII Deficiency itself are mild like epistaxis or skin abrasions and it does not cause excess bleeding. On the contrary. It is usually associated with thromboembolic complications that are sometimes life-threatening.

• FXII Signaling in Inflammatory Reactions

FXII partakes in complex receptor interactions that cooperatively regulate immune cell behavior and contribute to physiologic and pathophysiologic responses. Previous studies have demonstrated that FXII signaling induces the production of proinflammatory cytokine in monocytes, alveolar cells, dendritic cells, and macrophages. Those results jointly suggest that FXII signaling takes part in responses to various inflammatory diseases. It binds to domain 2 (D2) of uPAR (urokinase plasminogen activator receptor), regulating downstream pathways, including ERK1/2 and Akt2. FXII signaling leads to phosphorylation of ERK1/2, thus enhancing cell proliferation and angiogenesis. It also triggers the phosphorylation of Akt2, therefore up-regulating neutrophil trafficking and formation of neutrophil extracellular trap.

Fig. 2 FXII signaling increases mitogenic activity, angiogenesis, and immune cell reactivity. ^{2, 3}

FXII as a Target for Antibody Research and Development

As FXII is closely involved in thrombosis and proinflammatory responses, targeting FXII/ FXIIa has emerged as a potential therapeutic strategy, and anti-FXII antibodies are being designed and studied in full swing. A FXII-targeting monoclonal antibody has been studied for the prevention of attacks in patients with C1-esterase inhibitor-deficient hereditary angioedema. The results show that the antibody evidently decreases the occurrence of monthly attacks. Studies and trials on this anti-FXII antibody to evaluate its roles in different symptoms and diseases, including respiratory deterioration in patients with COVID-19 and idiopathic pulmonary fibrosis, are also being conducted.

Creative Biolabs offers many anti-FXII monoclonal antibody products. These antibodies are recombinantly expressed and could be used for various purposes.

REFERENCES

1. Jukema, Bernard Nico, Steven De Maat, and Coen Maas. "Processing of factor XII during inflammatory reactions." Frontiers in medicine 3 (2016): 52.
2. Rangaswamy, Chandini, et al. "The contact system in liver injury." Seminars in Immunopathology. Vol. 43. No. 4. Berlin/Heidelberg: Springer Berlin Heidelberg, 2021.
3. Distributed under Open Access license CC BY 4.0, without modification.