Antibodies to tissue‐type plasminogen activator (t‐PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t‐PA and possible implications in thrombosis

Abstract

Summary. Background: Patients with inflammatory bowel disease (IBD) have an increased prevalence of thromboembolic events. The pathogenetic mechanisms of these events include reduced fibrinolysis, which may be caused by antibodies to tissue-type plasminogen activator (t-PA). Objectives: To evaluate anti-t-PA antibodies in patients with IBD, considering clinical, biochemical and functional characteristics. Patients and methods: We immunoenzymatically measured anti-t-PA antibodies in plasma from 97 consecutive IBD patients and 97 ageand sex-matched healthy controls. We also assessed the antibody interactions with different epitopes of t-PA, the antibody inhibition on t-PA activity and the correlations with clinical features and other serum antibodies. Results: IBD patients had higher median anti-t-PA antibody levels (5.4 U mL )1 vs. 4.0 U mL )1; P < 0.0001): 18 patients were above the 95th percentile of the controls (OR 5.3; 95% CI 1.7-16.3; P < 0.003), and the six with a history of thrombosis tended to have high levels (6.9 U mL )1). Anti-t-PA antibody levels did not correlate with IBD type, activity, location or treatment, or with age, sex, acute-phase reactants or other antibodies. The anti-t-PA antibodies were frequently IgG1 and bound t-PA in fluid phase; they recognized the catalytic domain in 10 patients and the kringle-2 domain in six. The IgG fraction from the three patients with the highest anti-t-PA levels slightly reduced t-PA activity in vitro. Conclusions: The prevalence of anti-t-PA antibodies is high in IBD patients. By binding the catalytic or kringle-2 domains of t-PA, these antibodies could lead to hypofibrinolysis and contribute to the prothrombotic state of IBD.

Prothrombotic state and impaired fibrinolysis in bullous pemphigoid, the most frequent autoimmune blistering disease

“…Indeed, it has been reported that the risk of thrombosis is increased in patients with BP and we have found an annual incidence of venous thrombosis of 8% , which is clearly higher than that observed in the general elderly population (0·28–0·41% per year) . It is well known that the inflammatory response inhibits fibrinolysis, which contributes to the prothrombotic state seen in conditions such as sepsis , inflammatory bowel diseases and rheumatoid arthritis . However, to the best of our knowledge, no data are available concerning systemic fibrinolysis in BP patients, although it has been shown to be involved at local level in lesional skin in humans and experimental BP models .…”

Serological markers in inflammatory bowel disease

“…Levels of anti-t-PA antibodies were significantly higher in IBD patients as compared to healthy controls. Levels higher than the 95th percentile of the control values were detected in 18.6% of IBD patients [75].…”

Intra-Arterial Thrombolysis as an Ideal Treatment for Inflammatory Bowel Disease Related Thromboembolic Stroke: A Case Report and Review

“…The use of local thrombolysis for IBD thromboembolism may represent the most ideal treatment for these patients because of advantages such as reduced gastrointestinal bleeding risk, more rapid lysis of thromboembolisms, and lower doses of thrombolytic agents [9]. IBD patients have been recently documented to have large amounts of circulating antibodies to t-PA, which may decrease the efficacy of systemic therapy lending an additional advantage to the use of local thrombolysis [10]. Several cases of IBDrelated cerebral venous sinus thrombosis have been successfully treated with local therapy [11]; however, there is a paucity of literature on the successful treatment of IBD-related arterial ischemic stroke with local thrombolysis, as was demonstrated in this case report.…”