Microcalorimetry of Blood Serum Proteome: A Modified Interaction Network in the Multiple Myeloma Case

Abstract

Hereby we report on a novel approach in the study of multiple myeloma (MM), namely, differential scanning calorimetry (DSC) combined with serum protein electrophoresis. Distinct thermodynamic signatures describe the DSC thermograms of MM blood sera, in contrast to the unique profile found for healthy individuals. The thermal behavior of MM sera reflects a complex interplay between the serum concentration and isotype of the M protein and of albumin, and modified ligand- and/or protein-protein interactions, resulting in stabilization of globulins and at least a fraction of albumin. In all MM cases the 85 °C, transferrin-assigned transition is missing. A distinct feature of IgG isotype (κ and λ) DSC profiles only is the presence of a transition at 82 °C. A DSC-based classification of MM depicts two sets of melting patterns (MMt2 and MMt3 with two or three successive thermal transitions), and subsets within each set (MMt2(i) or MMt3(i), the subscript i = 1, 2 or 3 denotes the main transition being one of the three transitions). The results demonstrate the potential of DSC to monitor MM-related modifications of the serum proteome, even at low M protein concentrations, Bence Jones and importantly nonsecretory multiple myeloma cases, and prove DSC as a versatile tool for oncohematology.

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.…”

“…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 monitoring of the effect of endurance training and testosterone treatment on rat serum denaturation transition

“…In general, there are some similarities between denaturation DSC profiles of rat serum and human plasma/ serum of healthy individuals [2][3][4][5][6]. The temperature range of the whole transition is practically the same; however, the endothermic peak is more symmetric for rat than for human serum.…”

“…The thermally induced conformational transitions of proteins can be successfully investigated using differential scanning calorimetry (DSC). Recently, the DSC approach was applied to blood serum studies as a novel tool for disease diagnostics [2][3][4][5][6][7][8][9].…”

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.…”