Autoantibodies to plasminogen and tissue plasminogen activator in women with recurrent pregnancy loss

Abstract

SummaryReduced fibrinolytic activity has been described in primary antiphospholipid syndrome (PAPS), and may be responsible for thrombotic events. Antibodies to tissue type plasminogen activator (t-PA) or plasminogen (PLG) might contribute to the hypofibrinolytic state in autoimmune diseases, but the clinical significance of these antibodies is still unclear in recurrent pregnancy loss (RPL). The aim of this study is to evaluate the prevalence and clinical significance of anti-PLG and anti-t-PA antibodies in 87 patients with a history of RPL: 54 women with well-defined PAPS (mean age 32·5 years; range 26-38) and 33 women with unexplained RPL (mean age 30 years; range 24-39). IgG anti-PLG antibodies were found in 20 and four patients from the group with RPL/PAPS and unexplained RPL, respectively; IgG anti-t-PA antibodies were found in 11 and two patients from the above two groups, respectively. IgG anti-PLG antibodies were associated with the high risk of RPL (OR 7·2, P = 0·004), especially with RPL/PAPS (OR 11·2, P < 0·001) evaluated by Fisher's exact test, while IgG anti-t-PA were associated with RPL/PAPS (OR 10·0, P = 0·01) but not with RPL (OR 6·8, P = 0·06). A significant inhibition of exogenous fibrinolysis was observed by IgG fractions from patients with anti-PLG or anti-t-PA antibodies on microplates and on the human umbilical vein endothelial cells, compared with those from healthy controls. The prevalence of IgG anti-PLG antibodies was high in RPL patients, especially in RPL/PAPS, while the prevalence of IgG anti-t-PA antibodies was high in RPL/PAPS but not in RPL, and some of them might inhibit fibrinolysis in patients.

A nonfibrin macromolecular cofactor for tPA-mediated plasmin generation following cellular injury

“…[51][52][53] The existence of anti-tPA and antiplasminogen antibodies and altered fibrinolytic states in many autoimmune patients further connote that the cofactor ability of exposed protein aggregates mediates nonviable cell clearance and autoimmunity. [54][55][56][57] It would be interesting to determine whether tPA Ϫ/Ϫ and plasminogen Ϫ/Ϫ mice are predisposed to autoimmune diseases.…”

Increased Circulating Levels of Tissue-Type Plasminogen Activator Are Associated with the Risk of Spontaneous Abortion During the First Trimester of Pregnancy

“…Normal pregnancy is characterized by a hyper-coagulable state to prevent major hemorrhage during and after placental separation [24,25]. This hyper-coagulable state and impaired fibrinolytic capacity may contribute to the increased susceptibility of pregnant women to thrombosis of the uteroplacental vasculature and placental infarction [24][25][26], which have been associated with fetal loss [23,27].…”

Prevalence of Anticardiolipin Antibodies in Pregnancies with History of Repeated Miscarriages~!2010-03-24~!2010-06-11~!2010-08-26~!

“…The β2 glycoproteins act as a cofactor in the binding of antiphospholipid antibodies to anionic phospholipids, thus functioning as a natural anticoagulant and therefore any interference in this system may result in thrombosis [15]. In an animal model, spontaneous miscarriages were observed with passive transfer of purified anticardiolipin IgG [1, 16].…”