39 research outputs found
Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations
HLA-mismatches in hematopoietic stem-cell transplantation are associated with an
impaired overall survival (OS). The aim of this study is to explore whether the
Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to
identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE
are computationally predicted peptides derived from the patient’s mismatched-HLA
molecules that can be presented by donor-patient shared HLA. We retrospectively
scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II
(PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single
HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease.
These patients were divided into low and high PIRCHE-I and PIRCHE-II groups, based on
their PIRCHE scores, and compared using multivariate statistical analysis methods. The
high PIRCHE-II group had a significantly impaired OS compared to the low PIRCHE-II
group and the 10/10 reference group (HR: 1.86, 95%-CI: 1.02–3.40; and HR: 2.65,
95%-CI: 1.53–4.60, respectively). Overall, PIRCHE-II seem to have a more prominent
effect on OS than PIRCHE-I. This impaired OS is probably due to an increased risk
for severe acute graft-vs.-host disease. These data suggest that high PIRCHE-II scores
may be used to identify non-permissible HLA mismatches within single HLA-mismatched
hematopoietic stem-cell transplantations
Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications
© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio
Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions
Tania Rowley et al. present multivalent Fc molecules with enhanced avidity for Fc gamma receptors in order to improve the treatment of autoantibody-mediated human diseases. They found several key amino acids involved in Fc receptor binding interactions