Identification of differentially expressed serum proteins in infectious purpura fulminans

Abstract

Purpura fulminans (PF) is a life-threatening hemorrhagic condition. Because of the rarity and randomness of the disease, no improvement in treatment has been made for a long time. In this study, we assessed the serum proteome response to PF by comparing serum proteins between healthy controls and PF patient. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach was used after depleting 6 abundant proteins of serum. In total, 262 proteins were confidently identified with 2 unique peptides, and 38 proteins were identified significantly up- (≥ 2) or downregulated (≤ 0.5) based on spectral counting ratios (SpCPF/N). In the 38 proteins with significant abundance changes, 11 proteins were previously known to be associated with burn or sepsis response, but 27 potentially novel proteins may be specifically associated with PF process. Two differentially expressed proteins, alpha-1-antitrypsin (SERPINA1) and alpha-2 antiplasmin (SERPINF2), were validated by Western blot. This is the first study where PF patient and healthy controls are compared in a proteomic study to elucidate proteins involved in the response to PF. This study provides an initial basis for future studies of PF, and the differentially expressed proteins might provide new therapeutic targets to decrease the mortality of PF.

Figure 1

The results of Gene Ontology enrichment analysis. (a) Top 5 canonical biological processes based on the biological process analysis. (b) Top 5 molecular functions based on the molecular function analysis. (c) The cellular component enrichment result.

Figure 2

Validation by Western blot of two differentially expressed proteins SERPINA1 and SERPINF2. Serum samples from three healthy individuals (N), one PF patient (PF), and three burn sepsis patients (B) were used to perform WB. (a) and (c) Validation by same proteins WB and histograms visualize normalized mean relative-integrated-density ± standard deviation values. The significance of expression changes was performed by one-way ANOVA test: *P ≤ 0.05. (b) and (d) Validation by same volumes WB and histograms visualize normalized mean relative-integrated-density ± standard deviation values. The significance of expression changes was performed by one-way ANOVA test: *P ≤ 0.05.