Proteomics Reveals Age-Related Differences in the Host Immune Response to Sepsis

Sepsis
is commonly caused by community-acquired pneumonia (CAP) and may develop
into severe sepsis, characterized by multiple organ failure. The risk
of severe sepsis among CAP patients and subsequent mortality increases
sharply after the age of 65. The molecular mechanisms associated with
this age-related risk are not fully understood. To better understand
factors involved with increased incidence and mortality of severe
sepsis in the elderly, we used a nested case-control study of patients
enrolled in a multicenter observational cohort of 2320 participants
with CAP. We identified a total of 39 CAP patients 50–65 and
70–85 years old who did or did not develop severe sepsis. Plasma
samples were obtained on presentation to the emergency department
and prior to therapeutic interventions. A semi­quantita­tive
plasma proteomics workflow was applied which incorporated tandem immuno­affinity
depletion, iTRAQ labeling, strong cation exchange fractionation, and
nanoflow liquid chromatography coupled to high-resolution mass spectrometry.
In total, 772 proteins were identified, of which 58 proteins exhibit
statistically significant differences in expression levels among patients
with severe sepsis as a function of age. Differentially expressed
proteins are involved in pathways such as acute phase response, coagulation
signaling, atherosclerosis signaling, lipid metabolism, and production
of nitric oxide and reactive oxygen species. This study provides insight
into factors that may explain age-related differences in incidence
of severe sepsis in the elderly.