Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies

Abstract

We investigated whether changes to fibrinolysis were associated with other manifestations of systemic lupus erythematosus (SLE), including antiphospholipid (APL) antibody status, endothelial damage, and inflammation. Ninety-four patients (36 SLE patients, 58 healthy controls) were recruited from Tasmania, Australia. Circulating levels of plasminogen, α2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured, as well as APL antibodies (including lupus anticoagulant, anticardiolipin, and antibeta-2 glycoprotein-1 antibodies), soluble E-selectin, and interleukin-6. Whereas there was a significant decrease in plasminogen (patient vs. control; median) (210 vs. 444 ng/ml; P < 0.0001) and increase in α2-antiplasmin (0.53 vs. 0.09 μg/ml; P = 0.0007), there was increased t-PA (0.65 vs. 0.40 ng/ml; P = 0.0001) and decreased TAFI (8.8 vs. 10.0 ng/ml; P = 0.002) in SLE patients compared to healthy controls. Plasminogen was significantly associated with α2-antiplasmin (rho = -0.563, P < 0.001); TAFI (rho = 0.410, P = 0.011); soluble E-selectin (rho = 0.531, P = 0.001); and interleukin-6 (rho = 0.489, P = 0.002) in SLE patients; however, APL antibody status was not associated with any of the markers measured. This study has demonstrated that fibrinolysis is significantly altered in patients with SLE compared to controls, and associated with endothelial cell damage and inflammation, but not APL antibody status.

α2AP is associated with the development of lupus nephritis through the regulation of plasmin inhibition and inflammatory responses

“…[12][13][14][15][16][17][18][19] The increased circulating levels of PAP and α2AP, and the impaired fibrinolysis have been reported in patients with SLE. 7,8 These findings suggest that α2AP may play a critical role in the development of SLE.…”

“…Immune deposition, inflammatory responses, hypercoagulability, and thrombosis are associated with LN progression. [5][6][7][8] α2AP not only regulates PAP formation and fibrin deposition through plasmin binding and inhibition but is also associated with the production of several cytokines. 12,18 PAP reportedly induces the production of IgG and IgM in mononuclear cells, 37 and α2AP is associated with the production of IgE and the recruitment of immune cells.…”

“…2,4 It has been reported that autoantibody production, immune complex deposition, hypercoagulability, and thrombosis are associated with LN progression. [5][6][7][8] However, the precise mechanisms of LN pathogenesis have remained unclear.…”

Inflammation Is Associated With Platelet Coagulation Function Rather Than Enzymatic Coagulation Function in Patients With Takayasu Arteritis

“…Third, the specificity and sensitivity of the two tests were different. Some studies 22,23) have reported that fibrinolysis may be associated with inflammation. However, in accordance with the previous study by Girona,7) our study showed no correlations between FDP, EPL, LY30, CL30, and ESR, which indicated inflammation may not play a role in fibrinolysis in patients with TA.…”

Lytic Susceptibility, Structure, and Mechanical Properties of Fibrin in Systemic Lupus Erythematosus

“…Impaired fibrinolysis is another pathogenic mechanism in SLE, which may help explain why these patients are at increased risk of developing thrombosis (15). Defects in fibrinolysis are related to an increase in the levels of various fibrinolytic inhibitors, such as PAI-1 (16), α2-antiplasmain, TAFI (17), lipoprotein (a) (18), and a decrease of plasminogen activity (17) likely due to anti-plasminogen antibodies (19).…”