Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant

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.