Modification of the structural stability of human serum albumin in rheumatoid arthritis

• Published in: PloS one Vol. 18; no. 3; p. e0271008
• Main Authors: Lin, Hsien-Jung L., Parkinson, David H., Holman, J. Connor, Thompson, W. Chad, Anderson, Christian N. K., Hadfield, Marcus, Ames, Stephen, Zuniga Pina, Nathan R., Bowden, Jared N., Quinn, Colette, Hansen, Lee D., Price, John C.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.03.2023; Public Library of Science (PLoS)
• Subjects: Accessibility; Albumin; Amino acids; Arthritis; Arthritis, Rheumatoid; Binding; Biological products; Biological samples; Biology and Life Sciences; Biomarkers; Blood proteins; C-reactive protein; Calorimetry; Comparative analysis; Denaturation; Development and progression; Differential scanning calorimetry; Disease; Health aspects; Heat; Human serum albumin; Humans; Inflammation; Mass spectrometry; Mass spectroscopy; Medical diagnosis; Medicine and Health Sciences; Melt temperature; Patients; Peptides; Physical Sciences; Protein Binding; Protein interaction; Protein-protein interactions; Proteins; Proteomics; Research and Analysis Methods; Rheumatoid arthritis; Rheumatoid factor; Serum albumin; Serum Albumin, Human - chemistry; Serum proteins; Structural stability; Temperature; Thermal stability; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0271008

Differential scanning calorimetry (DSC) can indicate changes in structure and/or concentration of the most abundant proteins in a biological sample via heat denaturation curves (HDCs). In blood serum for example, HDC changes result from either concentration changes or altered thermal stabilities for 7–10 proteins and has previously been shown capable of differentiating between sick and healthy human subjects. Here, we compare HDCs and proteomic profiles of 50 patients experiencing joint-inflammatory symptoms, 27 of which were clinically diagnosed with rheumatoid arthritis (RA). The HDC of all 50 subjects appeared significantly different from expected healthy curves, but comparison of additional differences between the RA and the non-RA subjects allowed more specific understanding of RA samples. We used mass spectrometry (MS) to investigate the reasons behind the additional HDC changes observed in RA patients. The HDC differences do not appear to be directly related to differences in the concentrations of abundant serum proteins. Rather, the differences can be attributed to modified thermal stability of some fraction of the human serum albumin (HSA) proteins in the sample. By quantifying differences in the frequency of artificially induced post translational modifications (PTMs), we found that HSA in RA subjects had a much lower surface accessibility, indicating potential ligand or protein binding partners in certain regions that could explain the shift in HSA melting temperature in the RA HDCs. Several low abundance proteins were found to have significant changes in concentration in RA subjects and could be involved in or related to binding of HSA. Certain amino acid sites clusters were found to be less accessible in RA subjects, suggesting changes in HSA structure that may be related to changes in protein-protein interactions. These results all support a change in behavior of HSA which may give insight into mechanisms of RA pathology.