Systemic immune response alteration in patients with severe pressure ulcers.

Wound healing is a dynamic process involving tissue formation, debris removal and ultimately remodeling to restore skin integrity. Although wound healing is generally successful, this process can eventually fail, leading to chronic wounds like pressure ulcers (PUs), whose presence/absence has been considered by WHO as good indicator of patient's wellbeing and care quality. PUs are stratified into grades I to IV grades based on their severity, however, the existence of systemic markers predicting their clinical progression remains unexplored. Here, we performed a serum proteomic and transcriptomic profiling of 54 patients with PUs ranging from grade II to grade III-IV. Unsupervised clustering identified a distinctive immune-related proteomic and transcriptomic blood profile in high-grade PUs. Specifically, pathways controlled by inflammatory-linked genes such as IER3, TSLP, and TNFAIP6 (TSG-6) were found to be upregulated in high-grade PUs, together with a reduction in the levels of potent immunomodulators such as IL-10, IFNγ, MCP-2/CCL8, and CXCL-10 in serum from grade III-IV PUs patients. All together, indicating an altered inflammatory state in advanced PUs. This study provides novel insights regarding the use of omic approaches to find potential systemic biomarkers for the prediction of severity in PUs and could help to understand the molecular mechanisms underlying the chronic progression of this pathology.