Coagulation and fibrinolysis in patients with asthma

The research described in this thesis provides evidence that coagulation and fibrinolysis are altered in patients with asthma, and provides an overview of multiple hemostatic markers measured in plasma during several conditions. We have observed that under stable conditions, patients with asthma have a prothrombotic state in peripheral blood as compared to healthy controls. Furthermore, in healthy controls and in patients with stable asthma, prednisolone burst therapy results in a pro-coagulant state by increasing in vitro coagulation and reducing fibrinolysis. We also found that complete cessation of inhaled corticosteroids led to a loss of asthma control with increased asthma symptoms, but it did not lead to increased activation of hemostasis. Moreover, in epidemiologic studies, asthma has been associated with increased risk of pulmonary embolism, and we showed that current use of oral corticosteroids increased the risk of recurrent pulmonary embolism, whereas patients who stopped oral corticosteroids more than 6 months ago seemed to have a lower risk. Altogether, this thesis shows that patients with asthma, have increased pro-coagulant and reduced fibrinolytic activity, not only in stable conditions but also after treatment with (oral) corticosteroids. Given the frequent use of corticosteroids in clinical practice, clinicians should be aware of this risk when prescribing corticosteroids, since patients with asthma are likely to have a high risk to develop venous thromboembolism

Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8(+) T cells and MHC-II-dependent anergy of CD4(+) T cells. In this study, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity. DOI: http://dx.doi.org/10.7554/eLife.04433.00