Inhibition of the mTORC Pathway in the Antiphospholipid Syndrome

Inhibition of the mTORC Pathway in the Antiphospholipid SyndromeTo the Editor: Canaud et al. (July 24 issue) 1 describe the activation of the mammalian target of rapamycin complex (mTORC) through the phosphatidyl-inositol 3-kinase (PI3K)-AKT pathway in patients with the antiphospholipid syndrome, leading to chronic vascular lesions.In their retrospective analysis of 37 kidney-transplant recipients with the antiphospholipid syndrome, 10 patients who were treated with mTOR inhibitors had better graft survival, in line with in vitro studies.Since patients with catastrophic antiphospholipid syndrome have analogous vascular alterations, perhaps mTOR inhibitors could prevent vasculopathy in the antiphospholipid syndrome.However, venous thrombosis remains the most common thrombotic manifestation of the antiphospholipid syndrome, and mounting evidence suggests that mTOR inhibitors are prothrombogenic. 2Serum concentrations of von Willebrand factor were higher in kidney-transplant recipients who were treated with mTOR inhibitors 2 and in patients with the antiphospholipid syndrome. 3Among patients who were treated with mTOR inhibitors, as compared with those who did not receive mTOR inhibitors, the risk of thromboembolism was higher among kidney-transplant recipients (adjusted odds ratio, 3.0; 95% confidence interval, 1.3 to 7.0) 4 and among lung-transplant recipients. 5 We think an increased risk of thrombosis may offset the possible benefit of mTOR inhibitors among patients with the antiphospholipid syndrome.