Regensburg 2016 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 44: Biotechnology & Bioengineering
BP 44.3: Vortrag
Mittwoch, 9. März 2016, 15:45–16:00, H45
Microscale Thermophoresis to Diagnose alpha1-Antitrypsin Deficiency Disorder in Plasma — •Evgeniia V. Edeleva1,2, Therese Dau3, Susanne A.I. Seidel1, Dieter Jenne3, and Dieter Braun1,2 — 1Systems Biophysics, LMU, Munich, Germany — 2Quantitative Biosciences Munich (QBM), Munich, Germany — 3Comprehensive Pneumology Center (CPC), Munich, Germany
Conventional diagnostics of deficiency disorders is often limited to the measurement of concentration, not the affinity of the deficient component. In case of alpha1-antitrypsin (AAT) deficiency disorder, AAT plasma level is low in patients due to the genetic mutation. However, measured concentration of AAT does not correlate with the manifestation of symptoms. We hypothesized that AAT affinity to its target neutrophil elastase is different in plasma of different patients.
We developed a competition assay based on the physical phenomenon of thermophoresis. Our assay assesses the affinity of AAT in addition to its concentration. The measurement is performed directly in the natural milieu of blood plasma. The three-body binding problem is used to fit the experimental data.
The amplitude of thermophoresis correlates with symptoms manifestation in patients. Further measurements suggest a previously unknown component in plasma, capable of modulating the affinity of AAT to the target. Our work highlights the possibility of assay development in the natural environment of blood plasma with thermophoresis with the promise to significantly improve the management of AAT deficiency.