Studies On The Clinical Feature And IgG Subtype In A Patient With Acquired FⅩⅢ Deficiency Secondary To Systemic Lupus Erythematosus

Research background: Factor XIII is a plasma transglutaminase that participates in the final stage of the coagulation cascade. Thrombin-activated FXIII (FXIIIa) catalyzes the formation of covalent cross-links betweenγ-glutamyl andε-lysyl residues on adjacent fibrin chains in polymerized fibrin to form stable fibrin clot, therefore, FXIII is also named "fibrin stabilizing factor". The inhibitors of FXIII block the cross-linking of fibrin, which results in instability of the patients' fibrin clot, clinically, the condition can causes severe spontaneous recurrent bleeding. These disorders are quite rare, there are updated to a total of 34 cases of acquired inhibitors against FXIII. The causes of FXIII inhibitors emergence has not been clear. The development of FXIII inhibitors may be associated with the mechanism of immune tolerance. Most of FXIII inhibitors have been related to some autoimmune diseases, especially with systemic lupus erythematosus ,or prolonged drug ingestions including isoniazid, penicillin, phenytoin, practolol,and so on. In most cases reported, the FXIII inhibitors have been shown to be polyclonal or monoclonal IgG, with a prevalence of the IgG₁ subtype. We diagnosed the fourth FXIII inhibitor secondry to systemic lupus erythematosus, and studied the clinical features and immune characteristics.Part I The clinical features and diagnosis of acquired FXIII deficiencyObjective: To analyze the clinical and laboratory features of acquired FXIII deficiency secondry to systemic lupus erythematosus, determine the diagnosis of acquired FXIII inhibitor, and to improve the understanding toward acquired FXIII inhibitor; Methods: (1) Collecting and analyzing the patient's case history in details; (2) Screen tests for bleeding disorder, such as activated partial thromboplastin time (APTT) , Prothrombin time (PT) , fibrinogen, platelet count and function were performed ; FXIII inhibitor was identified by urea lysis assay and corrected urea lysis assay; Results: (1) The clinical manifestations of the patient were consistent with the phenotype of FXIII deficiency. Before presenting with multiple episodes of bleeding, the patient was diagnosed with systemic lupus erythematosus. There was no family history for bleeding or prior bleeding history; (2) APTT, PT, fibrinogen, platelet count and function were within normal range. Clots from the patients' plasma dissolved in 5M urea by 24 hours. Clots prepared from normal plasma were stable for 48 hours. The abnormal solubility of patients' plasma clot could not be corrected by normal pooled plasma, which identified the presence of FXIII inhibitor; Conclusion: We determined the clinical and laboratory diagnosis of acquired FXIII inhibitors in the patient with systemic lupus erythematosus. Clot solubility assay is the preliminary screening test of such hemorrhagic disease. Further clot solubility assay is helpful for determining the diagnosis.Part II IgG subtype assay of acquired FXIII inhibitor Objective: To identify FXIII inhibitor IgG subtype; Methods: TheIgG subtype of the FXIII inhibitors were identified by solid-phase binding combined with Western blot; Results: The result of Solid-phase binding combined with Western blot showed, when PVDF membrane incubated with patient's plasma , there was reactivity of the A subunit of FXIII with monoclonal anti-IgG₁ and IgG₄, but lacked the reactivity with monoclonal anti-IgG₂ or IgG₃; Conclusion: We definited the IgG subtype of FXIII inhibitor in the patient, and the subtype of the patient's inhibitor is IgG₁ and IgG₄ predominant.