Defining the role of xeno-directed and autoimmune .. (TRANSLINK)
Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves
Start date: Sep 1, 2013,
End date: Aug 31, 2017
TRANSLINK is a project devoted to assessing the mid-to long-term risk factors and improve the outcome of animal (bovine/porcine)-derived Bioprosthetic Heart Valve (BHV) implants. 300,000 patients/year benefit from BHV, a major healthcare problem (second most frequent cardiac surgery). BHV clinical outcome suffers from late dysfunctions restricting their application to older recipients. Based on a retrospective (already computerised) and prospective cohort of approximately 3,000 BHV recipients and control patients from 3 large EU cardiac surgery groups, TRANSLINK aims primarily to establish the possible role of recipients' immune response (IR) against BHV as a major cause to mid- to-long term clinical dysfunction. Precise molecular analysis of preimplantation BVH sugar moieties will be performed. Possible indirect side-effects on BHV endocarditis and host vessels inflammation are secondary end points. Serial and trans-sectional blood samples will be dispatched to a battery of highly specialised partner groups for testing anti-Gal, -Neu5Gc and -hyaluronic acid antibodies (Ig) using both validated and newly designed screening tools, glycan array patterns, and macrophages/NK responses. Data will be crossed with clinical outcome scores. Project design aims at delivering comprehensive recommendations in the time-frame of the grant. Fundamental basic science progress in the field of carbohydrate antigens is also expected. Furthermore, prevention (BHV from engineered animal source lacking major antigens) and treatment (bioabsorbants of deleterious Ig) oriented remedies as well as prospective biomarkers of longterm BHV deterioration will be set up by three first-class SMEs. TRANSLINK may strongly impact the treatment of heart valve diseases by improving morbid-mortality in patients with heart valves diseases and increasing the indication of BHV to younger patients.
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