PB0163 - Identification of Combined FXIII-C3 Autoantibodies in Patients with Acquired FXIII Deficiency and its Association with Immune Homeostasis

Background: Acquired FXIII deficiency is a rare hemolytic disease with up to 50% death rate. Currently, the disease pathogenesis and its correlation with immune homeostasis still remains elusive.

Aims: To identify a combined FXIII-C3 autoantibody existing in patients with acquired FXIII deficiency.

Methods: First, ELISA based assay was used to identify an autoantibody against FXIII exsits in patients sample. Secondly, protein A as well as FXIII coupled affinity column was applied to purify anti FXIII autoantibodies from patient plasma. Then WiElisa together with the hemolytic assay was used to analize the effect of anti-FXIII autoantibody on complement activation. Lastly, an in vivo mouse model and flow cytometry were used to analyze complement activation complement mediated T cell activation of FXIII-C3 deficient mice upon infection as well as infection triggerred autoantibody production.

Results: By analyzing the clinical cases in combination with in vitro molecular analysis and in vivo mouse models, we identified a combined FXIII-C3 autoantibody existing in patients with acquired FXIII deficiency. Such combined FXIII and C3 autoantibody, by neutralizing FXIII, causes abnormal coagulation and extensive bleeding. Meanwhile, it also complexed C3 and further blocked C3 cleavage by a preformed C3 convertase, thereby inhibiting the complement activation and complement-mediated adaptive immune responses. Such defect immune responses therefore increased the body's susceptibility to pathogenic infections. Exogenous infection in turn triggered further production of autoantibodies by altering the body's immune homeostasis, resulting in progressive depletion of FXIII, which forms a self-enhanced closed circle.

Conclusion(s): This work provided new ideas and new therapeutic guidance for better control and treatment of acquired FXIII deficiency.