| Autor: |
Kalaidopoulou Nteak S; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands., Völlmy F; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands., Lukassen MV; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands., van den Toorn H; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands., den Boer MA; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands., Bondt A; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands., van der Lans SPA; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht 3584 CH, The Netherlands., Haas PJ; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht 3584 CH, The Netherlands., van Zuilen AD; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht 3584 CH, The Netherlands., Rooijakkers SHM; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht 3584 CH, The Netherlands., Heck AJR; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht 3584 CH, The Netherlands.; Netherlands Proteomics Center, Utrecht 3584 CH, The Netherlands. |
| Abstrakt: |
Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events. |
