A pilot study evaluating protein abundance in pressure ulcer fluid from people with and without spinal cord injury

Abstract

Objective: To determine whether the biochemistry of chronic pressure ulcers differs between patients with and without chronic spinal cord injury (SCI) through measurement and comparison of the concentration of wound fluid inflammatory mediators, growth factors, cytokines, acute phase proteins, and proteases. Design: Survey. Setting: Tertiary spinal cord rehabilitation center and skilled nursing facilities. Participants: Twenty-nine subjects with SCI and nine subjects without SCI (>18 years) with at least one chronic pressure ulcer Stage II, III, or IV were enrolled. Outcome measures: Total protein and 22 target analyte concentrations including inflammatory mediators, growth factors, cytokines, acute phase proteins, and proteases were quantified in the wound fluid and blood serum samples. Blood samples were tested for complete blood count, albumin, hemoglobin A1c, total iron binding capacity, iron, percent (%) saturation, C-reactive protein, and erythrocyte sedimentation rate. Results: Wound fluid concentrations were significantly different between subjects with SCI and subjects without SCI for total protein concentration and nine analytes, MMP-9, S100A12, S100A8, S100A9, FGF2, IL-1b, TIMP-1, TIMP-2, and TGF-b1. Subjects without SCI had higher values for all significantly different analytes measured in wound fluid except FGF2, TGF-b1, and wound fluid total protein. Subject-matched circulating levels of analytes and the standardized local concentration of the same proteins in the wound fluid were weakly or not correlated. Conclusions: The biochemical profile of chronic pressure ulcers is different between SCI and non-SCI populations. These differences should be considered when selecting treatment options. Systemic blood serum properties may not represent the local wound environment.

Elevated levels of matrix metalloproteinases and chronic wound healing: an updated review of clinical evidence

“…The cellular and biochemical mechanisms leading to MMP dysregulation vary between aetiologies, 16 and may end up with various types or intensities of protease imbalance. 41,42,51 To demonstrate a strong correlation between MMP levels and the course of wound healing, all the published clinical trials assessed specific markers in well-defined cohorts of patients. As long as the same marker is followed in the same population, under the same conditions of analysis, it can reasonably be assumed that the interpretation of the results would be reliable.…”

Comprehensive Proteomic Profiling of Pressure Ulcers in Patients with Spinal Cord Injury Identifies a Specific Protein Pattern of Pathology

“…Although proteomics studies have been previously conducted on ulcers, [24][25][26] to the best of our knowledge, this is the first proteomics study comparing healthy and PU tissue from patients with SCI, which is important given that the biochemical profile of chronic PU is different between SCI and non-SCI populations. 27 Great efforts have been made in recent years to understand the mechanisms leading to the development of PUs in patients with SCI, including processes related to hemostasis, inflammation, proliferation, and remodeling. [28][29][30] Evidence has shown that the pathological process of PU formation is characterized by increased levels of proin- flammatory cytokines and proteases, 31 and also reactive oxygen species, 32,33 in addition to the development of a cellular senescent phenotype (keratinocytes, endothelial cells, fibroblasts, and macrophages).…”

Danger in the Intensive Care Unit

“…Interestingly, blunt trauma survivors demonstrate higher plasma S100A8/A9 level compared with nonsurvivors, suggesting a protective role of S100 proteins after trauma (66). S100B is released after traumatic brain injury and seems a promising marker for the diagnosis of brain damage or spinal cord injury (20,46). Release of mtDNA is also suggested to play a role in trauma.…”

“…HMGB1 consists of two homologous DNA-binding domains, the A-box and B-box, of which the B-box is related to the cytokine-like properties of HMGB1. Extracellular HMGB1 acts via a multitude of pathways, among others the binding of several pattern-recognition receptors and subsequent nuclear Nonsurvivors plasma HSPA12B" vs. survivors (8) Peritonitis: abdominal fluid S100A8/A9" vs. plasma (10) (Severe) sepsis þ septic shock: plasma HMGB1" during 1 wk after admittance, plasma HMGB1# nonsurvivors (7) HSP70 gene polymorphisms influence outcome (9) Trauma Trauma patients with hemorrhagic shock: plasma HMGB1" (15) Trauma patients, ventilated 2þ d, ISS 16: plasma HSP72": low plasma HSP72: survival# (18) Chronic spinal cord injury (SCI): S100A12, S100A8, S100A9 in wound fluid # vs. non-SCI patients (20) Trauma: plasma mtDNA" (21,39) Severe ARDS: S100A12 expression in lung", in BALF" (27,28) LPS inhalation in healthy volunteers: S100A12 in BALF" (27) Not investigated S100A8/A9 to S100A12 ratio in BALF: different between chronic and acute lung disease (28) Cardiac arrest Cardiac arrest patients: HMGB1" in CSF of patients with worse neurological outcome. No differences in serum (32) Cardiac arrest: plasma HSP70", correlated with immunoparalysis (34) Cardiac arrest: plasma S100A12", correlated with immunoparalysis (34) Cardiac arrest: plasma nDNA" (34) Acute myocardial infarction: serum HSP70", correlated with IL-6 and IL-8 (37) Cardiac arrest: S100B" in serum of patients with worse neurological outcome (32) Myocardial infarction: plasma mtDNA"…”