Calorimetry Outside the Box: A New Window into the Plasma Proteome

Abstract

Differential scanning calorimetry provides a new window into the plasma proteome. Plasma from normal individuals yields a characteristic, reproducible thermogram that appears to represent the weighted sum of denaturation profiles of the most abundant constituent plasma proteins. Plasma from diseased individuals yields dramatically different signature thermograms. Thermograms from individuals suffering from rheumatoid arthritis, systemic lupus, and Lyme disease were measured. Each disease appears to have a distinctive and characteristic thermogram. The difference in thermograms between normal and diseased individuals is not caused by radical changes in the concentrations of the most abundant plasma proteins but rather appears to result from interaction of as yet unknown biomarkers with the major plasma proteins. These results signal a novel use for calorimetry as a diagnostic tool.

Blood serum DSC analysis of well-trained men response to CrossFit training and green tea extract supplementation

“…The thermal profiles of heat capacity changes for aqueous solutions of human blood serum from athletes have been described and discussed in details earlier [37]. Comparing DSC curves of athletes serum diluted with distilled water (pH 6.5-7.0) with curves reported for serum/plasma of healthy persons where the final pH of solutions was in the range 7.2-7.5 [25][26][27][29][30][31][32][33][34][35][36], distinct differences are visible. The main origin of these differences is probably the thermal denaturation profile of fatty acid-free fraction of albumin.…”

“…The main origin of the local maximum (T 2 , Cp 2 ) in the serum denaturation peak is probably haptoglobin, the protein from alpha-2 globulins fraction [25,37]. Haptoglobin is an acute-phase protein, the synthesis of which is increased during inflammation.…”

“…Differential scanning calorimetry (DSC) has recently been found useful in the support of various medical diagnoses [25][26][27][28][29][30][31][32][33][34][35][36] by analysis of plasma or serum heat capacity changes in the temperature range of protein components thermal denaturation. DSC profiles of biofluids are able to reflect their modified composition, changes in thermal stability of major proteome components resulting from covalent modifications or binding interactions involving disease biomarkers.…”

Calorimetric and spectroscopic studies characterization of newborn rat’ blood serum after maternal administration of cyclophosphamide

“…It was shown by Garbet et al [4] that DSC curves of blood plasma represent the sum of weighted contributions of an individual protein. The major input to the measured heat effect is ascribed to albumins, gamma globulins including immunoglobulins such as IgG and IgM, a globulins with haptoglobin, a2 macroglobulin, and b globulins with transferrin.…”

Thermodynamic Signatures of Macromolecular Complexes ‒ Insights on the Stability and Interactions of Nucleoplasmin, a Nuclear Chaperone

“…Recently DSC was also recognized as a novel tool for disease diagnosis and monitoring [67][68][69][70]. Calorimetric studies of blood plasma/serum have revealed a typical DSC thermogram for healthy individuals, whereas pronounced changes in thermograms for diseased subjects, including oncopatients, have been reported.…”